Flotetuzumab was found to demonstrate antileukemic activity in patients with primary induction failure (PIF) and early-relapse acute myeloid leukemia (ER-AML), and the treatment appears tolerable with infrequent neurologic adverse events, according to results from an updated analysis of an ongoing open-label phase 1/2 study (ClinicalTrials.gov Identifier: NCT02152956). The preliminary findings were presented by Ibrahim Aldoss, MD, of the Gehr Family Center for Leukemia Research at City of Hope in Duarte, California, at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

CD123 is overexpressed on AML cells, including leukemia stem cells, as well as other hematological malignancies, said Dr Aldoss. Flotetuzumab is a humanized CD3 x CD123 bispecific T-cell engager that redirects T cells to kill tumor cells expressing CD123.

The open-label, single-arm, multicenter, phase 1/2 study previously identified the recommended phase 2 dosage of flotetuzumab as 500 ng/kg/d administered via continuous infusion in 28-day cycles following a step-up lead-in dose administered during cycle 1 in week 1 of treatment. The primary objective of the study was to assess safety and antileukemic activity of flotetuzumab in patients with PIF/ER-AML.

A total of 44 patients (PIF, n= 27; ER-AML, n=17) were included in the study. Median patient age was 63.5 years (range, 28.0-81.0), and most patient were men (70.5%). According to the European LeukemiaNet (ELN) 2017 risk stratification criteria, the majority of patients had nonfavorable risk (97.7%).

Evidence of antileukemic activity was documented in 59.1% of patients, with a median decrease of 81.0% in bone marrow blasts. Median time to first response was 1 cycle (range, 1-3).

The combined complete response rate (CR, <5% bone marrow blast) and CR with partial hematologic recovery (CRh) was 25.0% (PIF, 33.3%; ER-AML, 11.8%) and 31.8% when including CR with incomplete hematologic recovery (CRi). Among the 14 patients with CR/CRh/CRi, 8 patients subsequently underwent stem cell transplantation.

In addition, morphologic leukemia-free state was reported in 3 patients (PIF, n=1; ER-AML, n=2). Of the 10 patients with TP53 mutation, 5 were reported to have CRR/CRh/CRi, and 3 of those patients (60.0%) underwent stem cell transplantation.

For all patients who achieved CR/CRh/CRi, median duration of response was 8.13 months, and median overall survival was 10.7 months.

Cytokine release syndrome (CRS), the most frequently reported treatment-related adverse event, occurred in 100% of patients (n=44; all grade). One grade 3 CRS event occurred. Approximately half of CRS events (52%) occurred during step-up dosing in the first week of treatment, and the incidence of CRS progressively decreased over time.

Neurologic adverse events were reported as infrequent and of mild to moderate severity (all-grade headache, n=13; 29.5%). Neurologic treatment-related adverse events of grade 3 or more were confusional state (n=3) and dizziness (n=1).

Flotetuzumab demonstrated encouraging activity in patients with primary induction failure in early-relapse AML, a population with poor prognosis and high unmet medical need, Dr Aldoss concluded.

The study (ClinicalTrials.gov Identifier: NCT02152956) is currently enrolling patients.

Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Read more ofHematology Advisorscoverage of the ASH 2020 meeting by visiting theconference page.

Aldoss I, Uy G, Vey N, et al. Flotetuzumab as salvage therapy for primary induction failure and early relapse acute myeloid leukemia. Presented at: American Society of Hematology (ASH) 62nd Annual Meeting and Exposition; December 5-8, 2020. Abstract 331.

Read more here:
Antileukemic Activity Seen With Flotetuzumab in Primary Induction Failure, Early-Relapse AML - Hematology Advisor

Recommendation and review posted by Bethany Smith

Korean medical professionals have discovered a method to resolve postoperative complications of hematopoietic stem cell transplants (HSCT).

A team of researchers from Seoul National University Hospital (SNUH) said Monday that they had found a solution to prevent HSCT complications by effectively producing T lymphocytes progenitor-T cells (T cells hereafter) from HSCs.

The team said if a patient with a blood tumor receives T-cells with HSCT, it can reduce the fatal infection that may occur after transplantation.

This is because T-cells prevent various viral infections by attacking and destroying cancer cells. It is differentiated in the HSCT and developed through T-precursor cells in the thymus.

HSCT is a treatment transplanting healthy HSCs after removing cancer and HSCs from blood cancer patients. It is effective and important in curing various types of blood cancer, including bone marrow failure syndromes.

However, this method has a high risk of complications and can only be applied to some patients. Also, the lack of development of T-cells causes fatal complications, such as cytomegalovirus infections, even causing death.

The research team, led by Professor Shin Dong-yeop of the Department of Hematology-Oncology at the hospital, has successfully produced T cells from HSCs.

They extracted cord blood HSCs at high purity and created an artificial thymic organoid (ATO) culture using recombinant proteins and cytokines from humans. They focused on this idea, excluding the method which uses mice-derived proteins because it did not apply to humans.

As a result, they found that T cells increased more effectively by combining a low oxygen environment's physiological conditions. The phenomenon has been confirmed in multiple amounts by the leading antioxidant agent, ascorbic acid (vitamin C).

After 200 trials, we have found a method to cultivate progenitor T cells. This will improve therapeutic performance for patients who need transplants, and contribute to enhancing the T-cell therapy, which is developing at a fast rate, researchers said.

The results were published in Stem Cells, an international stem cell journal.

Originally posted here:
SNUH finds way to produce T-cells to prevent HSCT complications - Korea Biomedical Review

Recommendation and review posted by Bethany Smith

NHS England is to grant immediate access to AstraZenecas cancer drug Calquence (acalabrutinib) for certain patients with chronic lymphocytic leukaemia (CLL) after NICE backed it in first draft recommendations.

NICE recommended regular NHS funding for Calquence in CLL who are considered high-risk due to 17p deletion or TP53 mutations.

It is also recommended for adults with CLL who have had at least one previous treatment and only if AbbVie and Janssens class rival Imbruvica (ibrutinib) is their only suitable treatment option.

NHS England is granting access via an interim funding arrangement with AstraZeneca, which will end 30 days after publication of positive final guidance, after which treatment will be funded by routine commissioning budgets.

However the guidance has rejected Calquence for a third group of patients with untreated, non-high risk CLL who are unsuitable for treatment with chemotherapy.

AZ said it will provide further data analyses for continued discussions with NICE about this group of patients.

Calquence was approved in CLL by the EMA last month as monotherapy or in combination with Roches Gazyvaro (obinutuzumab).

In CLL, too many blood stem cells in the bone marrow become abnormal white blood cells, and these have difficulty in fighting infections.

As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells, and platelets. This could result in anaemia, infection, and bleeding.

B-cell receptor signalling through Brutons tyrosine kinase (BTK) is one of the essential growth pathways for CLL.

In B-cells, BTK signalling results in the activation of pathways necessary for growth: proliferation, trafficking, chemotaxis, and adhesion.

Calquence binds selectively to BTK, inhibiting its activity.

This is the second recommendation of a therapy for CLL in the space of a month in November it recommended AbbVie/Roches chemotherapy-free option of Venclyxto (venetoclax) and Gazyva.

NICEs decision allows for a 12-month fixed duration treatment option based on data from the phase 3 CLL14 trial.

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CLL patients in England to get AZ's Calquence after okay from NICE - - pharmaphorum

Recommendation and review posted by Bethany Smith

In 1932, when there was no known treatment for syphilis, the US Public Health Service (PHS) began a study into the disease at the Tuskegee Institute. The agency recruited 600 Black men into the project, primarily impoverished sharecroppers who had never visited a doctor before. Of this group, 399 had latent syphilis, while 201 others were disease-free. The participants were informed that they were being treated for bad blood, a colloquialism that was used at the time to describe numerous conditions.

The men were treated with placebos, such as aspirin and supplements, even after penicillin began to be recommended to treat syphilis in 1947, so that researchers could use them to follow the full progression of the disease. The men were not helped even as the disease progressed to late-stage infection, in which people experience a wide range of neurological symptoms including erratic behaviour, paralysis, sensory loss and eventually death. It can take up to 20 years from initial infection for these symptoms to manifest.

Details of the study were leaked to the press by a social worker and epidemiologist named Peter Buxtun in 1972. Buxtun had learned of the existence of the study in 1965 when he began working for the PHS and had unsuccessfully attempted to get it shut down twice over the following years. The story prompted public outrage and forced the study to finally be cancelled, four decades after it initially began.

By this stage, 28 of the participants had died from syphilis and 100 more had died of related complications. At least 40 of their spouses had been diagnosed with the disease and it had been passed down to 19 of the participants children.

Historical atrocities such as the Tuskegee experiment have left many people from communities of colour distrustful of the medical sector. Its a major problem, one that has become even more serious in the age of Covid-19.

People of colour have been shown to face higher mortality rates from the disease in both the US and UK. This is due to a multitude of intersecting demographic, geographical and socioeconomic factors, such as place of residence and occupational exposures. Extensive evidence also indicates that people of colour still do not receive the same levels of care as white people in community healthcare settings, which only exacerbates the matter.

Now, surveys in the US have shown that Covid-19 vaccine hesitancy is significantly higher among Black people than white people, with half of Black adults saying they wont take a Covid-19 vaccine. Likewise, a UK study has found that Black, Asian and minority ethnic (BAME) people were almost three times more likely to reject a Covid-19 vaccine for themselves and their children than the white population.

This mistrust is unsurprising given that US surveys have found medical staff to be less communicative with non-white patients than with white patients. A 2016 study even found that white medical students in the US were shockingly likely to believe Black patients experienced less pain than white patients.

Across the pond, BAME patients in the UK have reported lower satisfaction with the NHS and an overall less positive experience with doctors and nurses than white patients. Black women in the UK are five times more likely than white women to die during childbirth, and over 60% of Black people do not believe their health is as protected by the NHS as white peoples is.

Black people have generationally been hesitant to engage on initiatives like clinical trials and vaccines, says African Caribbean Leukaemia Trust (ACLT) co-founder and CEO Orin Lewis OBE. Thats historical, based on what has been done to the Black race for a long, long time throughout our history. People start to feel that if the medical establishment is going to trial something, theyll try it first on Black people, because were expendable. Whether thats true or not, it very much becomes folklore and trust becomes a problem.

People of colour are also less likely than white people to volunteer to take part in medical research. In the UK, 93% of people who signed up for the trials registry for the development of the Covid-19 vaccine were white.

People of colour have disproportionately suffered throughout the pandemic, in both the UK and US, but the legacy of institutional racism in medicine still leaves many mistrustful of the Covid-19 vaccine.

The medical establishment doesnt want to acknowledge this, they just kind of want to forget about it, says TruGenomix co-founder and chief scientific officer Dr Tshaka Cunningham. Thats not what certain communities are dealing with, particularly the African American community. That type of stuff leaves a psychological scar, but it can be overcome with rebuilding.

One way to heal these historic wounds, Cunningham says, is through the work of medical industry honest brokers. Honest brokers refer here to people of colour who are knowledgeable about medical matters, who can then share this insight with other members of their community.

Cunningham says: Lets say I were to bring a white male scientist in to talk to a group of African American church members. Theyre going to listen and be polite, but theyre not really going to trust it. When I deliver the same message, but Im just from the community, it gives a certain level of authenticity to it that helps them get over their distrust.

As a member of the Faith-based Genetic Research Institute, Cunningham goes into communities of colour predominantly African American churches to talk about genetics and genomics research and how and why people of colour can and should get involved. This year, these conversations have expanded to Covid-19 too.

Cunningham says: What I do almost daily is interface with different groups of people of colour, even in my local networks, about Covid-19 and how to stay safe. Ive done podcasts, Ive been on internet shows, Ive been on Instagram feeds with prominent hosts, talking specifically to minority communities about what we need to do to stay safe and debunking any myths that they have.

The burden here cannot fall on the honest broker alone its important work, but theres a limit to what can be expected of individual people facing up to an issue that requires institutional change. The medical industry at large, from pharmaceutical companies to public health organisations, needs to do far, far more.

Cunningham says: Once you have more Black and Brown people participating, it cant just be all on them to build the trust. Trust is a two-way street. People need to be really authentic and engaged and not view themselves as other or their patients as other.

I give some very simple solutions. Firstly, diversify the medical workforce, diversify the scientific research workforce and be very intentional about it. If you havent created opportunities or blocked certain groups from having opportunities to get training and to rise up in careers in these areas, then stop that process, because thats institutional racism.

Secondly, be authentic, engage with the community and allow the community to share in the profits that come out of their participation. Dont come to the Black and Brown community and say give us your health information and not give anything back.

I think a final piece is that just as the government has contributed to making it bad, they need to contribute to making it better. That will require some specific funding on things like cultural competency training.

The best thing to do would be some public health campaigns with scientists like myself alongside prominent sporting figures and celebrities. Lets say you took LeBron James and teamed him with me and some of my scientific colleagues that are people of colour and did a PSA about the vaccine that would send the right message to people.

The historical suffering of people of colour at the hands of the medical establishment isnt something that can be overcome overnight. The industry urgently needs to pay more credence to the concerns and fears of people of colour, in order to build the level of trust needed to ensure that vaccine uptake among ethnic minorities.

Theres no silver bullet, and things like grassroots community advocacy and engagement, diversifying the face of the industry and public health campaigns targeted at people of colour will all be necessary in ensuring the uptake of the vaccine and developing a medical industry that serves the needs of all patients.

Passive Thermal Protection and Cargo Security Solutions for the Global Supply Chain

28 Aug 2020

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Racism in the medical industry could harm the Covid-19 vaccine rollout - pharmaceutical-technology.com

Recommendation and review posted by Bethany Smith

Supporting stockmen in the region is a crucial part of the clubs activities and a fantastic display of young animals were brought forward to the selected venues Ballymena, Hilltown, Swatragh, Enniskillen, Keady, Camlough, Armoy, Dungannon, Markethill and Clogher. Given the restrictions we found ourselves in this year it was up to the market how they saw fit to distribute out the prize money.

Attracting good local support, the sales are always an excellent window of opportunity for commercial buyers to obtain Limousin cross cattle that are suitable for the current beef market. This year was no exception.

1st Prize 400kg 2100 (5.25p) sold by OKane Farm Ltd, Dunloy , Ballymena.

2nd Prize 350kg 1700 (4.85p) sold by Ian Lynn, Glenshesk Armoy.

3rd Prize 380kg 1820 (4.79p) - sold by Ian Lynn, Glenshesk Armoy.

1st Prize 270kg 900 (3.33p) sold by J Campbell, Ballyvaddy Road, Carnlough.

2nd Prize 210kg 700 (3.33p) sold by ST MACNISSIS College, Garron Tower.

3rd Prize 270kg 890 (3.29p) sold by J Campbell, Ballyvaddy Road, Carnlough

1st Prize 320kg 880 (2.75p) Sold by D Litter, Derrall Road, Portadown.

2nd Prize 260kg 700 (2.69p) Sold by D Litter, Derrall Road, Portadown.

1st Prize - 300kg 930 (3.10p) sold by N Hammond, Ballymaguire, Stewartstown.

2nd Prize 270kg 805 (2.98p) sold by N Hammond, Ballymaguire, Stewartstown.

1st Prize 318kg 1370 (4.30p) sold by Nigel Deens, Markethill

2nd Prize 340kg 1260 (3.71p) sold by J Rice , Armagh

1st Prize 244kg 770 (3.15p) sold by E McKeown, Crossmaglen

2nd Prize 284kg 880 (3.10p) sold by A Nugent , Keady

1st Prize 285kg 790 (2.77p) sold by Gabriel Emerson, Cushendall

2nd Prize 254kg 650 (2.56p) sold by Danny McBride, Ballycastle

1st Prize 230kg 720 (3.13p) sold by Gabriel Emerson, Cushendall

2nd Prize 210kg 650kg (3.10p) sold by Gabriel Emerson, Cushendall

1st Prize 308kg 1260 (4.09p) sold by Paul Faulkner

2nd Prize 356kg 1400 (3.93p) sold by Martin Diamond

1st Prize 282kg 930 (3.30p) sold by Paul Faulkner

2nd Prize - 452kg 1410 (3.12p) sold by Paul Faulkner

1st Prize 440kg 2250 (5.11p) sold by Darren McSorley, Omagh

2nd Prize 440kg 1900 (4.32p) Sold by Darren McSorley, Omagh

1st Prize 550kg 1250 (2.50p) sold by Ian Elliott, Enniskillen

2nd Prize 535kg 1100 (2.05p) sold by Jason Sawyers , Sixmilecross

1st Prize - 293.90 per 100 kilos sold by Alan Falloon, Armagh

2nd Prize - 282.60 per 100 kilos sold by P J McNally

1st Prize - 361.10 per 100 kilos sold by P J McNally

2nd Prize - 316.00 per 100 kilos sold by Joe Smith

1st Prize - 391.30 per 100 kilos sold by Kevin and Gerard McKee

2nd Prize - 314.80 per 100 kilos sold by Kevin and Gerard McKee

1st Prize -367.70 per 100 kilos sold by Thomas Nugent

2nd Prize 316.70 per 100 kilos sold by Kevin and Gerard McKee

1st Prize 326kg 1180 (3.62p) sold by Emmett Kelly, Augher, Co Tyrone

2nd Prize 392kg 1400 (3.57p) sold by Gordon Cutler, Florencecourt, Enniskillen

1st Prize 250kg 730 (2.92p) sold by Raymond McGovern, Derrylin

2nd Prize 270kg 740 (2.74p) sold by Raymond McGovern, Derrylin

Successful exhibitors were:

1st Prize Leo and Aaron Fearon

3rd Prize Leo and Aaron Fearon

The strength in the market for Limousin calves demonstrates how the breeds genetics continue to stand out within the sector.

The market demands fast finishing, efficient, low-cost cattle that produce carcases consistent in weight and quality.

It is a blueprint for the breed, one which it delivers extremely well and is the principle reason that buyers seek Limousin stock of all ages.

View post:
Local Limousin calves are on the money at recent suckled calf sales - Farming Life

Recommendation and review posted by Bethany Smith

VANCOUVER, BC / ACCESSWIRE / December 8, 2020 / FIORE GOLD LTD. (TSXV:F)(OTCQB:FIOGF) ("Fiore" or the "Company") is pleased to announce an updated resource and reserve estimate for its Pan open pit mine in White Pine County, Nevada.

Highlights:

Updated Proven and Probable mineral reserves of 24.0 million tons at a gold grade of 0.012 troy ounces per short ton ("oz/st") or 0.41 grams per tonne ("g/t") containing 290,500 ounces of gold (Table 1)

The updated mineral reserve estimate represents a 6% increase in contained gold ounces and fully replaces reserves mined since the last reserve update in September 2018

Updated Measured and Indicated mineral resources of 31.1 million tons at a gold grade of 0.014 oz/st (0.47 g/t) containing 427,400 ounces of gold (Table 2)

The updated mineral resource estimate is 99% of the resource estimate (effective February 10, 2017) at Fiore Gold's inception

An updated Life of Mine ("LOM") plan based on the updated reserve estimate extends the mine life at Pan by two years into 2025 at a mining rate of 14,000 tons per day of ore while maintaining a low life of mine strip ratio of 1.66:1

Tim Warman, Fiore's CEO commented, "Fiore's exploration team has once again added reserves and extended the mine life at the Pan Mine well into 2025. Our understanding of the geology and controls on mineralization at Pan has improved tremendously over the past three years and the team was able to successfully target new areas of mineralization particularly around the North Pit, as well as identifying potential new areas such as the Mustang target. The next program of resource and reserve expansion drilling is already underway at Pan, aimed at defining the resources that should see Pan continuing to operate for many years to come."

The updated reserve and resource estimates continue to support our strategy of replacing ounces at the Pan Mine by methodically and prudently investing internal cash flow to extend the mine life. At Fiore Gold's inception, the Pan Mine Proven and Probable mineral reserves and Measured and Indicated resources (effective February 10 and March 16, 2017 respectively) were 318,000 ounces and 430,000 ounces, respectively. Despite approximately three years of mining depletion, the updated 2020 Proven and Probable reserves and Measured and Indicated resources are 290,500 ounces (91% of original reserve) and 427,400 ounces (99% of original resource), respectively. The reserve and resource replacement has been achieved while spending approximately $1.5 million on exploration annually over the past three years. Importantly, we have achieved these results without diluting shareholders through additional equity raises or taking on corporate debt since the formation of the Company in 2017. We believe this disciplined approach distinguishes us from many of our peers.

Story continues

The goal of the recent drilling program and related reserve and resource update was primarily to convert Inferred ounces to reserve ounces. Pan Mine Proven and Probable mineral reserves now represent 77% of the Measured and Indicated resources, as compared to 61% of the last reserve update in September 2018. Future drilling programs will aim to replenish the Inferred category, particularly with newly identified targets like Mustang which to date are not included in any resource category. We believe our history of conversion and improved understanding of the geology bode well for our ability to convert Inferred resources going forward.

A Technical Report with the details of the updated resource and reserve estimate will be filed on SEDAR under the Company's profile within 45 days of the date of this news release.

Reserve and Resource Update

Table 1. Pan Mine Reserve Statement (effective June 30, 2020)

Reserve

Tons(000s)

Grade(oz/st)

Grade(g/t)

Contained Gold(Au koz)

Proven

11,426

0.014

0.47

158.3

Probable

12,031

0.011

0.38

132.2

Proven + Probable

23,457

0.012

0.42

290.5

Probable Leach Pad Inventory(recoverable)

26

Total Proven and Probable

317

Reserves stated in the table above are contained within an engineered pit design following the US$1,575/oz Au sales price Lerchs-Grossmann pit. Date of topography is June 30, 2020;

In the table above and subsequent text, the abbreviation "st" denotes US short tons;

Mineral Reserves are stated in terms of delivered tons and grade before process recovery. The exception is leach pad inventory, which is stated in terms of recoverable Au ounces;

Allowances for external dilution are applied.

Costs used include an ore mining cost of US$2.09/st, a waste mining cost of $1.97/st, an ore processing and G&A cost of US$3.13/st;

Reserves for Argillic (soft) ore are based upon a minimum 0.003 oz/st Au internal cut off grade ("CoG"), using a US$1,575/oz Au sales price and a Au Recovery of 80%;

Reserves for Silicic (hard) ore are based upon a minimum 0.004 oz/st Au Internal CoG, using a US$1,575/oz Au sales price and a Au Recovery of 60%;

Mineral Reserves stated above are contained within and are not additional to the Mineral Resource, the exception being stockpile and leach pad inventory; and,

Numbers in the table have been rounded to reflect the accuracy of the estimate and may not sum due to rounding.

Gold prices have increased significantly from the $1,250/oz level used in the previous reserve update in 2018 and we have reflected this increase in the $1,575/oz gold price used in the 2020 reserve update. Using a higher gold price naturally pulled in some areas of lower grade ore which in turn resulted in a lower average grade for the reserve estimate than in the previous 2018 reserve estimate. The grade reduction is not expected to materially impact run-rate production in fiscal 2021.

Table 2. Pan Mine Resource Statement (effective June 30, 2020)

Resource(incl. reserve)

Tons/(000s)

Grade(oz/st)

Grade(g/t)

Contained Gold(Au koz)

Measured

11,416

0.015

0.53

175

Indicated

19,714

0.013

0.44

252

Measured +Indicated

31,130

0.014

0.47

427

Inferred

3,726

0.016

0.56

61

Mineral Resources are not Mineral Reserves and do not have demonstrated economic viability. There is no certainty that any part of the Mineral Resources estimated will be converted into Mineral Reserves;

In the table above and subsequent text, the abbreviation "st" denotes US short tons;

Resources stated as contained within a constrained pit shell; pit optimization was based on an assumed gold price of US$1,700/oz, Silicic (hard) ore recoveries of 60% for Au and an Argillic (soft) ore recovery of 80% for Au, an ore mining cost of US$2.09/st, a waste mining cost of $1.97/st, an ore processing and G&A cost of US$3.13/st, and pit slopes between 45-50 degrees;

Resources are reported using an internal gold cut off grade of 0.003 oz/st Au for blocks flagged as Argillic altered or as unaltered and a cutoff of 0.004 oz/st Au for blocks flagged as Silicic altered.; and,

Numbers in the table have been rounded to reflect the accuracy of the estimate and may not sum due to rounding.

The updated Pan Mineral Resource Estimate ("MRE") estimate was carried out by APEX Geoscience Ltd. ("APEX") as part of an updated Feasibility Study led by SRK Consulting (U.S.) Inc. ("SRK"), the same firm who completed the February 2017 Pan Mine Feasibility Study.

The difference in resource grade vs reserve grade is a result of dilution incorporated in the engineered pit design that constrains the reserve estimate.

Gold mineralization at Pan occurs in near-vertical pipes and bodies of silicified solution breccia localized at the Pilot Shale-Devils Gate Limestone contact adjacent to the Branham Fault, or in stratiform-like breccia bodies and zones that run parallel or sub-parallel to the folded Pilot Shale-Devils Gate contact.

The drillhole database used to calculated the resource and reserve estimates is comprised of 1,452 exploration drillholes completed from 1978 to 2016 by previous operators (totaling 380,081 ft) and 267 holes completed from 2018 to 2020 by Fiore Gold (totaling 107,460 feet), yielding a total of 95,181 sample/interval entries.

The MRE was calculated using a block model size of 20 ft (X) by 20 ft (Y) by 20 ft (Z). APEX estimated the gold grade for each block using Ordinary Kriging with locally varying anisotropy to ensure grade continuity in various directions is reproduced in the block model. The block model was partially diluted by estimating a waste grade for the portions of the outer blocks overlapping the edge of the estimation domain boundaries using composites within a transition zone along the outer edge of the mineralized estimation domains. The waste grade was then proportionately combined with the estimated grade for the portion of the block within the mineralized domain to obtain a final grade for each overlapping block. The partially diluted block model was utilized for resource pit optimization. The MRE is reported as undiluted and only includes blocks or portions of blocks within the estimation domains.

Details regarding the methodology used to calculate the MRE and the reserve estimate will be documented in a Technical Report which will be filed on SEDAR and available on the Company's website within 45 days.

Technical Disclosure

The scientific and technical information relating to Fiore Gold's properties contained in this press release was approved by J. Ross MacLean, Fiore Gold's Chief Operating Officer and a "Qualified Person" under National Instrument 43-101, except for the information relating to the Pan Mine reserve and resource updates.

Michael B. Dufresne, M.Sc., P.Geol., P.Geo., President and Senior Principal of APEX Geoscience Ltd. and a 'Qualified Person' for the purpose of National Instrument 43-101 Standards of Disclosure for Mineral Projects of the Canadian securities administrators ("NI 43-101") has approved the disclosure of the scientific and technical information regarding the Pan Mine Resource update in this news release.

Justin Smith, P.E. Mining BSc., SME-RM, a Senior with SRK Consulting (U.S.) Inc. and a 'Qualified Person' for the purpose of National Instrument 43-101 Standards of Disclosure for Mineral Projects of the Canadian securities administrators ("NI 43-101") has approved the disclosure of the scientific and technical information regarding the Pan Mine Reserve update in this news release.

A description of the key assumptions, parameters and methods used to estimate mineral reserves and resources at the Pan Mine, as well as data verification procedures and a general discussion of the extent to which the estimates of scientific and technical information may be affected by any known legal, political or other relevant factors relating to the potential development of the mineral resources or mineral reserves, will be included in the report titled "NI 43-101 Updated Technical Report on the Pan Gold Mine, White Pine County, Nevada", with an effective date of June 30, 2020, which is being prepared by Michael Dufresne,, P.Geol., P.Geo., Justin Smith, P.E., RM-SME., Deepak Malhotra, RM-SME, Valerie Sawyer, RM-SME, Fredy Henriquez, MSc., RM-SME, and Michael Iannacchione, P.E..

Corporate Strategy

Our corporate strategy is to grow Fiore Gold into a 150,000 ounce per year gold producer. To achieve this, we intend to:

continue to grow gold production at the Pan Mine, while increasing the resource and reserve base

advance exploration and development of the nearby Gold Rock project

acquire additional production or near-production assets to complement our existing operations

On behalf of FIORE GOLD LTD.

"Tim Warman"Chief Executive Officer

Contact Us:

info@fioregold.com1 (416) 639-1426 Ext. 1www.fioregold.com

Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.

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Fiore Gold Reports Two Year Mine Life Extension at Its Pan Mine, Nevada - Yahoo Finance

Recommendation and review posted by Bethany Smith

CAMBRIDGE, England--(BUSINESS WIRE)--Crescendo Biologics Ltd (Crescendo), the drug developer of novel, targeted T cell enhancing therapeutics, today announced that it has expanded its global, multi-target discovery and development collaboration with Takeda Pharmaceutical Company Limited (Takeda) after Crescendo achieved its sixth technical milestone.

Under its ongoing collaboration and license agreement, Crescendos proprietary transgenic platform and engineering expertise is being used to build Humabody-based therapeutics against certain targets selected by Takeda.

The collaboration expansion gives Takeda access to a range of Crescendos half-life extension Humabodies for use with its two Humabody programmes, previously licensed in November 2018 and July 2019, and Humabody programmes Takeda licenses in the future during the term of the collaboration expansion.

This is the sixth technical milestone achieved by Crescendo in its collaboration with Takeda. Crescendo has successfully delivered novel oncology-targeted Humabody lead molecules using its robust in-house discovery process.

Theodora Harold, CEO of Crescendo, commented:

Crescendo has again demonstrated its ability to deliver differentiated Humabody molecules against specific targets selected by Takeda, on schedule. The expansion of our collaboration, together with the achievement of this sixth milestone, further validates the excellent work being done at Crescendo to progress the next generation of differentiated cancer therapies.

Loc Vincent, Head, Oncology Drug Discovery Unit, Takeda, commented:

Our fruitful collaboration with Crescendo continues to show great progress. We are delighted to expand our work together, drawing on Takedas vast oncology drug discovery experience and Crescendos expertise in developing optimally constructed Humabody molecules to quickly advance novel therapeutics with transformative treatment potential towards the clinic.

-Ends-

About Crescendo BiologicsCrescendo Biologics is a clinical stage T cell enhancing company. Crescendo develops potent, truly differentiated Humabody therapeutics with a focus on innovative, targeted T cell approaches in oncology.

Leading its proprietary pipeline, Crescendo Biologics has developed CB307, a novel CD137 x PSMA bispecific for the selective activation of tumour-specific T cells exclusively within the tumour microenvironment. CB307 is designed to achieve a longer lasting anti-cancer effect whilst avoiding systemic toxicity.

The Companys ability to develop multi-functional Humabody therapeutics is based on its unique, patent protected, transgenic mouse platform generating 100% human VH domain building blocks (Humabody VH). These robust molecules can be configured to engage therapeutic targets in such a way that they deliver novel biology and superior bio-distribution. This results in larger therapeutic windows compared to conventional IgG approaches. Humabody-based formats can also be applied across a range of non-cancer indications.

Crescendo Biologics is located in Cambridge, UK, and is backed by blue-chip investors including Sofinnova Partners, Andera Partners, IP Group, Takeda Ventures, Quan Capital and Astellas.

For more information, please visit the website: http://www.crescendobiologics.com

Visit link:
Crescendo Biologics Expands its Ongoing Collaboration with Takeda - Business Wire

Recommendation and review posted by Bethany Smith

Creatine is a compound produced by the body and found naturally in a variety of foods.

Creatine supplements are often used to enhance athletic performance, increase strength, and reduce muscle damage (1, 2, 3).

Creatine monohydrate, which consists of a creatine molecule paired with a water molecule, is the most common and best-researched type of creatine supplement (1).

Other types are also available. They combine creatine with other compounds intended to increase absorption or boost performance, such as magnesium, citric acid, malic acid, or hydrochloride.

However, not all creatine supplements are created equal, and with so many options available, finding a high quality supplement can be challenging.

The products included in this article were selected based on the following criteria:

Here are 10 of the best creatine supplements of 2020.

General price ranges with dollar signs ($ to $$$) are indicated below. One dollar sign means the product is rather affordable, whereas three dollar signs indicate a higher price range.

Generally, prices range from $0.10$3.13 per serving, or $8.21$56.37 per tub, package, or bottle, though this may vary depending on where you shop.

Note that serving sizes vary by product.

Pricing guide$ = under $0.50 per serving$$ = $0.50$1 per serving$$$ = over $1 per serving

Price: $

Thorne Research is a company focused on producing high quality, sustainably sourced supplements.

This unflavored product contains 5 grams of creatine per serving and is free of gluten, soy, dairy, yeast, and other major allergens.

Its also NSF Certified for Sport, meaning that it has undergone third-party testing to ensure that its free of harmful contaminants and specific substances that are banned for athletes.

Price: $

With 5 grams of creatine monohydrate per serving, this product from Klean Athlete is ideal for those seeking a simple yet high quality creatine supplement.

Like most other Klean Athlete products, Klean Creatine is NSF Certified for Sport to ensure that it meets strict quality standards.

Its also unflavored and can be easily mixed into smoothies, shakes, and juices.

Price: $

This high quality supplement is a convenient and cost-effective way to help ramp up your intake of creatine.

It contains 5 grams of creatine monohydrate per serving and is formulated without any additives or extra ingredients, such as gluten, sugar, soy, dairy, or yeast.

Plus, BulkSupplements can also provide a Certificate of Analysis (CoA) upon request, which is a detailed document that provides information on the quality, strength, and specifications of a product.

Price: $$

Available in flavors like orange, grape, and fruit punch, this creatine powder from Muscle Tech can be a delicious addition to your workout routine.

It not only includes 5 grams of creatine per scoop but also delivers 1 gram of branched-chain amino acids (BCAAs), which are a type of amino acid often used by athletes to boost performance and reduce fatigue (4).

It also contains around 36 grams of carbs per serving, which is thought to help maximize creatine retention (5).

Price: $

This product is not only free of artificial colors, flavors, and sweeteners but also made without any genetically modified organisms (GMOs) and contains just one ingredient.

Its likewise certified vegan and certified gluten-free, making it a great option for those with food allergies or dietary restrictions.

Additionally, Naked Creatine by Naked Nutrition contains 5 grams of creatine monohydrate and can be easily dissolved in your favorite pre- or post-workout beverage.

Price: $$$

With 550 calories, 54 grams of protein, and 3.2 grams of creatine per serving, this multipurpose protein powder is perfect for bulking.

It comes in a vanilla crme flavor, which adds a pleasant taste to high calorie shakes and smoothies.

Its also NSF Certified for Sport, making it a good choice for athletes seeking a safe supplement free of banned substances.

Price: $

Featuring 5 grams of creatine monohydrate per serving, this supplement is specifically designed to promote energy production and muscle growth.

In addition to being certified kosher and vegan-friendly, its certified by Informed-Choice, a third-party organization that tests sports supplements for banned substances.

Plus, its produced in a facility that has been certified for following good manufacturing practices (GMPs), which ensure that supplements are produced according to strict quality standards set by the Food and Drug Administration (FDA).

Price: $

If you prefer the convenience and ease of pills over powders, these creatine capsules from Life Extension may be a good choice.

Each serving contains approximately 1 gram of creatine, and capsules are certified non-GMO and gluten-free.

Life Extension also provides a CoA for all products to help ensure quality and promote product transparency.

Price: $$

This Power+ product from PurAthlete is made for athletes looking to increase endurance, strength, and stamina.

It features 3.3 grams of Creatine MagnaPower, a type of creatine thats combined with magnesium to enhance absorption and energy production.

Its also NSF Certified for Sport and produced in a GMP-certified facility, meaning that you can feel confident that youre getting a safe, high quality supplement.

Price: $$$

Whether youre a casual gym-goer or competitive athlete, this pre-workout supplement from Proven4 Sport can help boost your exercise routine.

Each serving contains 2 grams of creatine monohydrate, along with a blend of other ingredients like B vitamins, caffeine, and amino acids.

Whats more, this product is NSF Certified for Sport and available in a variety of flavors, including blue raspberry, cherry limeade, fruit punch, and watermelon.

When selecting a creatine supplement, be sure to check the ingredient label carefully and look for products free of artificial flavors, sweeteners, colors, and fillers whenever possible.

However, note that some supplements may contain added carbs or protein, which can help increase the retention of creatine (5).

You should also pay close attention to the dosage of creatine supplements.

Its generally recommended to start with a loading phase of 2025 grams per day for 57 days to increase muscle stores of creatine, followed by a maintenance dosage of 35 grams daily thereafter (6).

If possible, you should also choose supplements that have undergone third-party testing and are certified by organizations like NSF or Informed-Choice to ensure safety and quality.

Some companies may also provide a CoA upon request, which offers detailed information about the purity and potency of products.

Check out these two articles to help make supplement shopping a breeze:

Creatine supplements are available in a variety of forms, flavors, and dosages.

When picking the right product for you, be sure to check the ingredient label and dosage carefully.

Ideally, you should also purchase products that have undergone third-party testing or provide a CoA available upon request.

See the original post here:
The 10 Best Creatine Supplements in 2020 - Healthline

Recommendation and review posted by Bethany Smith

Carlo Wolters, director of Netherlands power company EPZ, has called for an extension to the operation of the Borssele NPP beyond 2033. Alternatively EPZ seeks the construction of two new large reactors at the site to enable the Netherlands to meet its energy and climate goals.

Wolters made the statement at a parliamentary debate on the role of nuclear power in the Dutch energy system, where he presented a position paper, EPZ Vision 2033 A Strategy for Dutch Nuclear Energy, which was first published on 28 November.

EPZ is currently the only Dutch party with the experience to operate a nuclear power plant in combination with a wind and solar park, the document says.

EPZ sees nuclear as a key climate-neutral source of energy, which should continue to be used in the Netherlands. For this there are two options plant life extension and/or newbuild.

As to life extension, EPZ said a letter from EPZ about this has already been sent to Minister for Economic Affairs and Climate Policy Eric Wiebes and the House of Representatives. The condition set by EPZ is that any market risk is covered in the business case, the Vision paper says. It envisages extending operation of the Borssele NPP by 10 to 20 years.

On the newbuild option, EPZ favours building two new Generation III 1500MWe units before the mid-1930s at the Borssele site. A precondition is the choice of a proven (and licensed) reactor design for which the permit and consultation processes can be completed on time, the paper notes. Subsequently, during construction, no changes to design and regulations will be made. Finally it is necessary that any market risk in the business case is covered by the government.

EPZ says construction of an existing, approved reactor concept is feasible. Generation III reactors have three times the power of Borssele and are therefore very interesting economically. They can now be purchased from various suppliers and there is sufficient space for new construction in the immediate vicinity of the existing nuclear plant, EPZ adds.

The addition of two identical nuclear power stations (with phased completion) seems the most optimal strategy, the paper notes. With an adequate project progression, the costs of a new Generation III reactor are 8-10 billion and the construction time is about eight years. With a combination of these two options, climate-neutral capacity could be in use by the mid-2030s. Borssele could even be 3500MWe, with an availability of 90%. This covers approximately 25% of current Dutch electricity demand. The paper adds: A fully climate-neutral energy system by 2050 remains within reach, even if electricity consumption continues to increase.

EPZ notes that around 2030, CO2 emissions from the electricity sector will be between 11 and 25 megatonnes. If EPZ keeps the existing nuclear power plant open and builds two new ones, the savings will be 13 megatonnes.

In September Minister of Economic Affairs and Climate Eric Wiebes said in a letter to members of parliament that more nuclear power may join solar and wind in the Dutch energy mix after 2030, in particular small modular reactors (SMRs). The International Energy Agency (IEA) said in a recent energy policy review that lifetime extension "could prove of great benefit to maintain the low-carbon generation...and the know-how of the Dutch nuclear sector".

See the article here:
EPZ calls for continued nuclear power in the Netherlands - Nuclear Engineering

Recommendation and review posted by Bethany Smith

New York, Dec. 10, 2020 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Global Military Aircraft Modernization and Upgrade and Retrofit Market 2020-2024" - https://www.reportlinker.com/p04483599/?utm_source=GNW 61 bn during 2020-2024 progressing at a CAGR of 3% during the forecast period. Our reports on military aircraft modernization and upgrade and retrofit market provides a holistic analysis, market size and forecast, trends, growth drivers, and challenges, as well as vendor analysis covering around 25 vendors. The report offers an up-to-date analysis regarding the current global market scenario, latest trends and drivers, and the overall market environment. The market is driven by the incorporation of CNS systems in aircraft and emergence of SVAB. In addition, incorporation of CNS systems in aircraft is anticipated to boost the growth of the market as well. The military aircraft modernization and upgrade and retrofit market analysis includes type segment and geographical landscapes

The military aircraft modernization and upgrade and retrofit market is segmented as below: By Type Combat aircraft Transport aircraft Others

By Geographical Landscapes North America APAC Europe MEA South America

This study identifies service life extension of military aircraft fleets as one of the prime reasons driving the military aircraft modernization and upgrade and retrofit market growth during the next few years.

The analyst presents a detailed picture of the market by the way of study, synthesis, and summation of data from multiple sources by an analysis of key parameters. Our military aircraft modernization and upgrade and retrofit market covers the following areas: Military aircraft modernization and upgrade and retrofit market sizing Military aircraft modernization and upgrade and retrofit market forecast Military aircraft modernization and upgrade and retrofit market industry analysis

Read the full report: https://www.reportlinker.com/p04483599/?utm_source=GNW

About ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

__________________________

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The Global Military Aircraft Modernization and Upgrade and Retrofit Market is expected to grow by $ 2.61 bn during 2020-2024 progressing at a CAGR of...

Recommendation and review posted by Bethany Smith

The report gives a complete investigation of the CONTROLLED INTELLIGENT PACKAGING, PRESERVATION AND SHELF-LIFE EXTENSION industry and key market improvements. The exploration record comprises of past and figure showcase data, prerequisite, territories of use, value strategies, and friends portions of the main organizations by topographical district. The CONTROLLED INTELLIGENT PACKAGING, PRESERVATION AND SHELF-LIFE EXTENSION market report separates the market size, by volume and worth, depending upon the kind of utilization and area.

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Some of the players in CONTROLLED INTELLIGENT PACKAGING, PRESERVATION AND SHELF-LIFE EXTENSION Market are Cargill Inc. (U.S),Nestl (Switzerland),DuPont (U.S),Tetra Pak (Switzerland),International Paper Co (U.S),Crown Holdings Inc. (U.S),Bemis Company Inc. (U.S),Tyson Foods Inc. (U.S)

With everything taken into account, the CONTROLLED INTELLIGENT PACKAGING, PRESERVATION AND SHELF-LIFE EXTENSION market report offers inside and out profile and information data life structures of driving CONTROLLED INTELLIGENT PACKAGING, PRESERVATION AND SHELF-LIFE EXTENSION organizations.

The CONTROLLED INTELLIGENT PACKAGING, PRESERVATION AND SHELF-LIFE EXTENSION market report presents a point by point estimation of the market through complete appraisal, fantastic experiences, and bona fide expectations managing the CONTROLLED INTELLIGENT PACKAGING, PRESERVATION AND SHELF-LIFE EXTENSION market size. It depends on attempted and tried methodologies alongside convictions in the event of the estimate made accessible. In this manner the nitty gritty investigation of CONTROLLED INTELLIGENT PACKAGING, PRESERVATION AND SHELF-LIFE EXTENSION market fills in as a repository of examination and information for each part of the market, especially concerning nearby markets, innovation, classifications, and use.

The report involves the estimation of the Global CONTROLLED INTELLIGENT PACKAGING, PRESERVATION AND SHELF-LIFE EXTENSION Market. The accompanying Industry is appeared to advance with a critical ascent in the Compound Annual Growth Rate (CAGR) during the conjecture time frame attributable to different elements driving the market.

The extent of the report stretches out from market situations to similar valuing between significant players, cost and benefit of the predetermined market areas. The numerical information is upheld up by factual apparatuses, for example, SWOT investigation, Porters Five Analysis, PESTLE examination, etc.

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Key Features of the Report:

The report provides granular level information about the market size, regional market share, historic market (2015-2019) and forecast (2020-2026).

The report covers in-detail insights about the competitors overview, company share analysis, key market developments, and their key strategies.

The report outlines drivers, restraints, unmet needs, and trends that are currently affecting the market

The report tracks recent innovations, key developments and startups details that are actively working in the market.

The report provides plethora of information about market entry strategies, regulatory framework and reimbursement scenario.

The report analyses the impact of socio-political environment through PESTLE Analysis and competition through Porters Five Force Analysis in addition to recent technology advancements and innovations in the market.

What is the Impact of Covid-19 Outbreak on the CONTROLLED INTELLIGENT PACKAGING, PRESERVATION AND SHELF-LIFE EXTENSION Market?

Optimistic Scenario: COVID-19 is contained by May or June, With Normalcy Returning to Global

Operations through the End of Q2.

Conservative Scenario: COVID-19 Remains Prevalent, with Continued Impacts Lasting into Q4.

Estimated Impact of the Coronavirus (COVID-19) Epidemic on the Global CONTROLLED INTELLIGENT PACKAGING, PRESERVATION AND SHELF-LIFE EXTENSION Market.

CONTROLLED INTELLIGENT PACKAGING, PRESERVATION AND SHELF-LIFE EXTENSION Market Size in 2020.

Corporate Strategy the Manufacturers Should Be Thinking About Right Now.

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Controlled Intelligent Packaging, Preservation and Shelf-Life Extension Market to Witness Widespread Expansion During 2020 to 2026 Cargill Inc....

Recommendation and review posted by Bethany Smith

Growing emphasis on the food safety and longer shelf life has played an important role in the development of ingredients that aid in food preservation. These ingredients vary from simple water content to salt or sugar to chemicals like antioxidants and are used to prevent growth of microorganisms, thereby delaying the spoilage process. In terms of origin, food safety and shelf life extension ingredients can be synthetic or natural in nature.

Food preserving ingredients have been an integral part of kitchen aisles in the form of lemon, ginger, vinegar, spices, salt and sugar. Their traditional utilization was replaced by synthetic ingredients with increasing commercialization of the food industry in past decades. However, with the dissemination of knowledge related to harmful effects of synthetic ingredients, currently, the industry is witnessing a prominent shift toward natural ingredients for food safety and shelf life extension.

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Shelf Life Extension Ingredients Market Notable Developments

Shelf Life Extension Ingredients Market Dynamics

Clean-Label Trend Fuels Synthetic to Natural Transition in Food Ingredient Landscape

Naturally sourced ingredients have gained significant traction as consumer preference for natural products continues to surge. In terms of effectiveness, natural preservatives are superior in delivering greater protection and longer shelf life. As they work with equivalent efficiency and are healthful in nature, adoption of naturally sourced ingredients is increasing consistently as compared to the synthetic options.

Natural ingredients such as antimicrobials or antioxidants have additional potential health benefits also. Well aware of the increasing consumer demand for natural food products that are without artificial ingredients, manufacturers in the food ingredient market are introducing bio-based or naturally sourced food safety ingredients.

Frozen Foods Drive Demand for Specialized Food Safety Ingredients

Ranging from salads to sauces or ready meals to rice, a plethora of food products are available in frozen forms. As the demand for fresh and frozen foods increase across the globe, food manufacturers are seeking innovative ways to introduce novel food safety ingredients to extend the shelf life of frozen foods.

Manufacturers in the food safety and shelf life extension ingredient market are introducing ingredients specific to refrigerated products. Along with providing safety, these ingredients are label friendly and help in reducing sodium content while enhancing consumers sensory experience.

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Shelf Life Extension Ingredients Market Regional Outlook

North America presents lucrative opportunities for the Shelf Life Extension Ingredients Market on the back of buoyancy in regions the food and beverage industry and presence of leading F&B companies.

The market is likely to witness increasing opportunities in the developing countries of Asia pacific. These countries are witnessing huge demand for frozen foods, RTD food and beverages and processed food, thereby presenting higher potential for the market in the future.

Shelf Life Extension Ingredients Market Segmentation

The Shelf Life Extension Ingredients Market is segmented into following,

Based on type, Shelf Life Extension Ingredients Market can be segmented in,

Based in function, Shelf Life Extension Ingredients Market can be segmented in,

Based on application, Shelf Life Extension Ingredients Market can be segmented in,

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TMR Research is a premier provider of customized market research and consulting services to business entities keen on succeeding in todays supercharged economic climate. Armed with an experienced, dedicated, and dynamic team of analysts, we are redefining the way our clients conduct business by providing them with authoritative and trusted research studies in tune with the latest methodologies and market trends.

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Shelf Life Extension Ingredients Market Demand, Growth, Opportunities and Analysis Of Top Key Player Forecast To 2028 - Murphy's Hockey Law

Recommendation and review posted by Bethany Smith

Novartis already knew that adding Kisqali to endocrine therapy can help premenopausal patients with HR-positive, HER2-negative advanced breast cancer live longer. Now, it knows exactly how long.

Kisqali plus endocrine therapy helped pre- and perimenopausal women with HR+/HER2- disease live a median 58.7 months, according to phase 3 data presented at the San Antonio Breast Cancer Symposium's (SABCS') virtual annual meeting. Thats compared with 48 months forendocrine therapy alone, translating to a 24% reduction in the risk of death for the Kisqali regimen.

Deploy Configurable, Fit-for-Purpose ePRO Solutions, Fast.

Clinical Inks enhanced Lunexis ePRO+ module streamlines processes through a flexible, unified platform that allows patients and sites a high degree of optionality.

Jeff Legos, Ph.D., Novartis head of oncology drug development, called Kisqalis new survival showing very impressive given that these patients historically survived for around three years after treatment. Patients in the control arm of the Monaleesa-7 trial appeared to live longer because some went on to receive Kisqali afteran initial survival readout, which showed a 29% reduction in the risk of death.

The Kisqali regimen also extended the time period before patients need follow-up chemotherapy by about 31%. Patients on the Kisqali combo lived a median 50.9 months before their first post-treatment chemo, while the time was 36.8 months for endocrine therapy alone.

The survival benefit was similar in a subgroup of patients who took a nonsteroidal aromatase inhibitor (NSAI) as part of their endocrine therapy. The death risk reduction in those patients was 20%, as the Kisqali group also lived a median 58.7 months, versus 47.7 months for the control arm.

RELATED:ASCO: Novartis' Kisqali posts first-in-class survival win in younger women

Thats the most relevant data for Kisqali in this patient population,given that its only approved by the FDA in combination with an NSAI. The Monaleesa-7 study also tested tamoxifen as an endocrine option, but, in those patients, researchers identified ahigher-than-expected increase in an abnormal heart rhythm called QT prolongation.

Novartis has now reported statistically significant life extension benefits for Kisqali in premenopausal women in the Monaleesa-7 trial and in postmenopausal women in the Monaleesa-3 study.The Monaleesa-2 program testing Kisqali in combination with the endocrine therapy letrozole in previously untreated patients is expected to have overall survival data in the second half of 2021.

The current Monaleesa-7 study was carried out in patients who hadnt been previously treated witha CDK4/6 inhibitor or endocrine therapy, but it did allowprevious treatment with chemotherapy.

Biomarker victory over Ibrance

In a cherry on top of Kisqalis 2020 SABCS data cake, Novartis unveiled a pooled analysis of the three trials showing the CDK4/6 inhibitor reduced the risk of disease progression or death in three of the four main subtypes of breast cancer.

In patients with the more traditional Luminal A and Luminal B subtypes, where Legos said patients have done reasonably OK with solo endocrine therapy, adding Kisqali significantly slashed the risk of disease progression or death by 37% and 48%, respectively, across the three trials.

The best news for Kisqali, though, according to Legos, came fromthe HER2-enriched subtype, which makes up about 15% of the HR+/HER2- breast cancer population. This subgroup traditionally had not done very well on endocrine therapy alone and hence it can be sort of deemed as a poor prognostic factor, Legos explained.

But in this group, the Kisqali-endocrine pairing cut the risk of disease progression or death by 61%.

RELATED:ESMO: Lilly's Verzenio pressures Pfizer with practice-changing win in early breast cancer

The showing in this subtype is important because its the first time a CDK4/6 inhibitor combo topped endocrine therapy alonein these women, Legos said. Three years ago at the SABCS event, a retrospective analysis of the Paloma-2 trial found Pfizers market-leading CDK4/6 inhibitor, Ibrance, didnt benefit the HER2-enriched subtype, he pointed out.

I think this just addsto the growing body of evidence that these mixed results that were seeing in both the metastatic setting, as well as in the adjuvant setting, may suggest that not all of the CDK4/6 inhibitors are equal, Legos said in an interview ahead of the data presentation.

Indeed, Ibrance has repeatedly failed in several HR+/HER2- breast cancer trials. The most famous is the Paloma-3 trial, which showed adding Ibrance to endocrine therapy in metastatic patients didnt significantly beat endocrine therapy at extending patients lives.

RELATED:Pfizer's Ibrance kisses early breast cancer hopes goodbye with 2nd study failure

And, in the postsurgery setting known as adjuvant treatment, Ibrance recently failed to lengthen the time early breast cancer patients could live without invasive disease returning. It didnt deliver a benefit in a wider patient group or in a high-risk subgroup.

Meanwhile, updated data from the phase 3 monarchE trial presented at this years SABCS showed the adjuvant pairing of Eli Lillys rival CDK4/6 inhibitor Verzenio and endocrine therapy reduced the risk of invasive disease after surgery by 28.7% in high-risk patients with an extended follow-up of 19 months.

CDK4 versus CDK6

Novartis has been attributing Kisqalis better efficacyas compared to Ibrancesto its drugs higher inhibition of CDK4 over CDK6. While CDK4 is more widely expressed in breast cancer cells, CDK6 is found more in the bone marrow; plus, CDK4 plays a greater role in cell proliferation and growth, Legos explained. Verzenio also inhibits CDK4 to a higher degree.

Kisqali isnt omnipotent, though. The Novartis drug didnt show a tumor progression improvement in the basal-like subtype. Legos said this represents a small group of patients whose tumors resemble triple-negative breast cancer. These patients constitute an average 3% of participants across the three Monaleesa trials, which Legos said is reflective of the real-world makeup.

Novartis is running a separate trial called Natalee, hoping to show that Kisqali on top of endocrine therapy works as an adjuvant treatment for both intermediate and high-risk patients. Data from that trial areexpected in 2022.

More here:
SABCS: Novartis touts Kisqali's 5-year breast cancer survival, advantage over Pfizer's Ibrance - FiercePharma

Recommendation and review posted by Bethany Smith

HAMBURG, GERMANY / ACCESSWIRE / December 9, 2020 / Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) and the life science company Sartorius announced today that they have entered into a partnership with the recently established Curexsys GmbH, a Goettingen, Germany-based technology leader specialising in the emerging field of therapeutic exosomes.

Curexsys delivers a proprietary isolation technology for exosomes based on a traceless immune-affinity process. This process is different from commonly used antibody-based processes and enables the company to overcome a key hurdle in exosome preparation, i.e. remaining antibodies in the final preparation. Curexsys is founded by Herbert Stadler, a serial biotech entrepreneur, and Jens Gruber, a former group leader of Medical RNA Biology who is going to lead Curexsys as Chief Scientific Officer.

Under the terms of the agreement, Evotec and Curexsys will collaborate with the production of Human Mesenchymal Stem Cells ("MSCs"), which serve as a source for exosomes. These are small vesicles that are naturally released from a cell. They contain proteins, nucleic acids and metabolites, which carry information from secreting to receiving cells. Exosomes have immunomodulatory and anti-inflammatory effects, which makes them a promising novel approach for innovative regenerative therapies, as therapeutics in age-related conditions, but also for diagnostic purposes. Curexsys aims to develop targeted approaches for a variety of diseases, initially focusing on Sicca Syndrome, commonly known as "dry eye", an inflammatory condition affecting 14% to 17% of the adult population for whom there is currently no effective treatment available.

The collaboration combines Evotec's industry-leading induced Pluripotent Stem Cell ("iPSC") platform with Curexsys' proprietary technology to selectively isolate exosomes. Sartorius will support Curexsys to set up a GMP-compliant and scalable manufacturing platform.

Furthermore, Evotec and Sartorius have formed a consortium to jointly invest in Curexsys' 8.2 m seed financing round with Evotec acquiring an equity stake of approx. 37% in Curexsys and Sartorius of approx. 21%.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, commented: "Therapeutic exosomes hold significant promise for regenerative medicine and beyond. Steadily increasing evidence suggests that exosomes derived from stem cells can aid tissue repair and engineering vesicles could carry drugs to diseased tissues. These efforts have been held back by a dearth of standardised methods to isolate and study vesicles. Combining Evotec's industrial-grade iPSC and PanOmics platforms with Curexsys' proprietary exosome isolation technology and Sartorius' ability to translate these into a fully GMP-compliant process is a unique opportunity to build the leading exosome company in the industry."

Dr Ren Faber, Head of Sartorius' Bioprocess Solutions Division, said: "With our integrated portfolio of manufacturing solutions Sartorius is the 'go-to' partner for developers of such new modalities when it comes to implementing GMP-compliant, flexible production processes. We are very much looking forward to contributing our proven and scalable technology platform to Curexsys process and help them achieve their next milestones faster."

Dr Jens Gruber, Chief Scientific Officer of Curexsys, added: "We are very happy that we were able to form such a consortium with industry leaders in their field. This unique constellation gives Curexsys an optimal starting position to advance our technologies for highly specific isolation of exosomes and to rapidly approach therapeutic applications."

About Exosomes and CurexsysExosomes are extracellular, nanoscale vesicles that are actively secreted from cells to transfer information to neighbouring cells and distant tissues. Exosomes carry information of secreting to receiving cells utilising proteins, nucleic acids and metabolites. MSC-derived exosomes function as paracrine mediators that limit inflammation, reprogram immune cells, and activate endogenous repair pathways, recapitulating to a large extent the therapeutic effects of parental MSCs. Exosomes hold potential as diagnostics, as therapeutics and cosmeceuticals. More than 100 clinical trials involving exosomes are currently ongoing, demonstrating their broad therapeutic potential.

Curexsys is a Goettingen, Germany-based start-up company founded by molecular biologist Dr Jens Gruber and the biochemist and serial entrepreneur Dr Herbert Stadler. With a scalable and semi-automated proprietary system for traceless immune-affinity cell sorting, Curexsys aims to become the leading supplier for clinical grade exosomes in regenerative medicine and anti-aging therapies.

About Evotec and iPSCInduced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from adult cells. Pluripotent stem cells hold great promise in the field of regenerative medicine. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease.

Evotec has built an industrialised iPSC infrastructure that represents one of the largest and most sophisticated iPSC platforms in the industry. Evotec's iPSC platform has been developed over the last years with the goal to industrialise iPSC-based drug screening in terms of throughput, reproducibility and robustness to reach the highest industrial standards, and to use iPSC-based cells in cell therapy approaches via the Company's proprietary EVOcells platform.

ABOUT SARTORIUSThe Sartorius Group is a leading international partner of life science research and the biopharmaceutical industry. With innovative laboratory instruments and consumables, the Group's Lab Products & Services Division concentrates on serving the needs of laboratories performing research and quality control at pharma and biopharma companies and those of academic research institutes. The Bioprocess Solutions Division with its broad product portfolio focusing on single-use solutions helps customers to manufacture biotech medications and vaccines safely and efficiently. The Group has been annually growing by double digits on average and has been regularly expanding its portfolio by acquisitions of complementary technologies. In fiscal 2019, the company earned sales revenue of some 1.83 billion euros. At the end of 2019, more than 9,000 people were employed at the Group's approximately 60 manufacturing and sales sites, serving customers around the globe.

SARTORIUS CONTACTPetra KirchhoffHead of Corporate Communications and Investor Relations+49 (0)551.308.3684 petra.kirchhoff@sartorius.comwww.sartorius.com

ABOUT EVOTEC SEEvotec is a drug discovery alliance and development partnership company focused on rapidly progressing innovative product approaches with leading pharmaceutical and biotechnology companies, academics, patient advocacy groups and venture capitalists. We operate worldwide and our more than 3,400 employees provide the highest quality stand-alone and integrated drug discovery and development solutions. We cover all activities from target-to-clinic to meet the industry's need for innovation and efficiency in drug discovery and development (EVT Execute). The Company has established a unique position by assembling top-class scientific experts and integrating state-of-the-art technologies as well as substantial experience and expertise in key therapeutic areas including neuronal diseases, diabetes and complications of diabetes, pain and inflammation, oncology, infectious diseases, respiratory diseases, fibrosis, rare diseases and women's health. On this basis, Evotec has built a broad and deep pipeline of more than 100 co-owned product opportunities at clinical, pre-clinical and discovery stages (EVT Innovate). Evotec has established multiple long-term alliances with partners including Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CHDI, Novartis, Novo Nordisk, Pfizer, Sanofi, Takeda, UCB and others. For additional information please go to http://www.evotec.com and follow us on Twitter @Evotec.

FORWARD LOOKING STATEMENTSInformation set forth in this press release contains forward-looking statements, which involve a number of risks and uncertainties. The forward-looking statements contained herein represent the judgement of Evotec as of the date of this press release. Such forward-looking statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.

SOURCE: Evotec AG via EQS Newswire

View source version on accesswire.com:https://www.accesswire.com/620112/Evotec-and-Sartorius-Partner-with-Start-Up-Curexsys-on-IPSC-Based-Therapeutic-Exosome-Approach

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Evotec and Sartorius Partner with Start-Up Curexsys on IPSC-Based Therapeutic Exosome Approach - BioSpace

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After 15 years of unrelenting work, a team of scientists from Gladstone Institutes has now discovered a potential drug candidate for heart valve disease that works in both human cells and animals and is ready to move toward a clinical trial. Their findings were just published in the journal Science.

"The disease is often diagnosed at an early stage and calcification of the heart valves worsens over the patient's lifetime as they age," says Gladstone President and Director of the Roddenberry Stem Cell Center Deepak Srivastava, MD,who led the study. "If we could intervene early in life with an effective drug, we could potentially prevent the disease from occurring. By simply slowing the progression and shifting the age of people who require interventions by 5 or 10 years, we could avoid tens of thousands of surgical valve replacements every year."

This also applies to the millions of Americansabout one to two percent of the populationwith a congenital anomaly called bicuspid aortic valve, in which the aortic valve only has two leaflets instead of the normal three. While some people may not even know they have this common heart anomaly, many will be diagnosed as early as their forties.

"We can detect this valve anomaly through an ultrasound," explains Srivastava, who is also a pediatric cardiologist and a professor in the Department of Pediatrics at UC San Francisco (UCSF). "About a third of patients with bicuspid aortic valve, which is a very large number, will develop enough calcification to require an intervention."

Srivastava's research into heart valve disease started in 2005, when he treated a family in Texas who had this type of early-onset calcification. All these years later, thanks to the family's donated cells, his team has finally found a solution to help them and so many others.

A Holistic Approach in the Hunt for a Therapy

Members of the family treated by Srivastava had disease that crossed five generations, enabling the team to identify the causea mutation in one copy of the gene NOTCH1. Mutations in this gene cause calcific aortic valve disease in approximately four percent of patients and can also cause thickening of valves that trigger problems in newborns. In the other 96 percent of cases, the disease occurs sporadically.

"The NOTCH1 mutation provided a foothold for us to figure out what goes wrong in this common disease, but most people won't have that mutation," says Srivastava. "However, we found that the process that leads to the calcification of the valve is mostly the same whether individuals have the mutation or not. The valve cells get confused and start thinking they're bone cells, so they start laying down calcium and that leads to hardening and narrowing of the valves."

In the hunt for a treatment, the group of scientists chose a novel, holistic approach rather than simply focusing on a single target, such as the NOTCH1 gene.

"Our goal was to develop a new framework to discover therapeutics for human disease," says Christina V. Theodoris, MD, PhD, lead author of the study who is now completing her residency in pediatric genetics at Boston Children's Hospital. "We wanted to find promising therapies that could treat the disease at its core, as opposed to just treating some specific symptoms or peripheral aspects of the disease."

When Theodoris first joined Srivastava's lab at Gladstone, she was a graduate student at UCSF. At the time, they knew the NOTCH1 gene mutation caused valve disease, but they didn't have the tools to study the problem further, largely because it was very difficult to obtain valve cells from patients.

"My first project was to convert the cells from the patient families into induced pluripotent stem (iPS) cells, which have the potential of becoming any cell in the body, and turn them into cells that line the valve, allowing us to understand why the disease occurs," says Theodoris. "My second project was to make a mouse model of calcific aortic valve disease. Only then could we start using these models to identify a therapy."

One Drug Candidate Rises to the Top

For this latest study, the scientists searched for drug-like molecules that could correct the overall network that goes awry in heart valve disease and leads to calcification. To do so, they first had to determine the network of genes that are turned on or off in diseased cells.

Then, they used an artificial intelligence method, training a machine learning program to detect whether a cell was healthy or sick based on this network of genes. They subsequently treated diseased human cells with nearly 1,600 molecules to see if any drugs shifted the network in the cells enough that the machine learning program would reclassify them as healthy. The researchers identified a few molecules that could correct diseased cells back to the normal state.

"Our first screen was done with cells that have the NOTCH1 mutation, but we didn't know if the drugs would work on the other 96 percent of patients with the disease," says Srivastava.

Fortunately, Anna Malashicheva, PhD, from the Russian Academy of Sciences, had collected valve cells from over 20 patients at the time of surgical replacement, and Srivastava struck up a fruitful collaboration with her group to do a "clinical trial in a dish."

"We tested the promising molecules on cells from these 20 patients with aortic valve calcification without known genetic causes," Srivastava adds. "Remarkably, the molecule that seemed most effective in the initial study was able to restore the network in these patients' cells as well."

Once they had identified a promising candidate in cells in a dish for both NOTCH1 and sporadic cases of calcific aortic valve disease, Srivastava and his team did a "pre-clinical trial" in a mouse model of the disease. They wanted to determine whether the drug-like molecule would actually work in a whole, living organ.

The scientists confirmed that the therapeutic candidate could successfully prevent and treat aortic valve disease. In young mice who had not yet developed the disease, the therapy prevented the calcification of the valve. And in mice that already had the disease, the therapy actually halted the disease and, in some cases, led to reversal of the disease. This finding is especially important since most patients aren't diagnosed until calcification has already begun.

"Our strategy to identify gene networkcorrecting therapies that treat the core disease mechanism may represent a compelling path for drug discovery in a range of other human diseases," says Theodoris. "Many therapeutics found in the lab don't translate well to humans or focus only on a specific symptom. We hope our approach can offer a new direction that could increase the likelihood of candidate therapies being effective in patients."

The researchers' strategy relied heavily on technological advancements, including human iPS cells, gene editing, targeted RNA sequencing, network analysis, and machine learning.

"Our study is a really good example of how modern technologies are facilitating the kinds of discoveries that are possible today, but weren't not so long ago," says Srivastava. "Using human iPS cells and gene editing allowed us to create a large number of cells that are relevant to the disease process, while powerful machine learning algorithms helped us identify, in a non-biased fashion, the important genes for distinguishing between healthy and diseased cells."

"By using all the knowledge we gathered over a decade and a half, combined with the latest tools, we were able to find a drug candidate that can be taken to clinical trials," he adds. "Our ultimate goal is always to help patients, so the whole team is very pleased that we found a therapy that could truly improve lives."

About the Research Project

The paper, "Network-based screen in iPSC-derived cells reveals therapeutic candidate for heart valve disease,"was published online by Science on December 10, 2020.

Other authors include Ping Zhou, Lei Liu, Yu Zhang, Tomohiro Nishino, Yu Huang, Sanjeev S. Ranade, Casey A. Gifford, Sheng Ding from Gladstone; Aleksandra Kostina from the Russian Academy of Sciences; and Vladimir Uspensky from the Almazov Federal Medical Research Centre in Russia.

The work was funded by the California Institute of Regenerative Medicine; the National Heart, Lung, and Blood Institute; and the National Center for Research Resources. Gladstone researchers also received support from the Winslow Family, the L.K. Whittier Foundation, The Roddenberry Foundation, the Younger Family Fund, the American Heart Association, several programs and fellowships at UCSF, residency programs from Boston Children's Hospital and the Harvard Medical School, the Uehara Memorial Foundation, and a Howard Hughes Medical Institute Fellowship of the Damon Runyon Cancer Research Foundation.

About Gladstone Institutes

To ensure our work does the greatest good, Gladstone Institutes focuses on conditions with profound medical, economic, and social impactunsolved diseases. Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease.

Media Contact: Julie Langelier | Assistant Director, Communications | [emailprotected] | 415.734.5000

SOURCE Gladstone Institutes

https://gladstone.org

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A Potential Therapy for One of the Leading Causes of Heart Disease - PRNewswire

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A new clinical trial offers the most compelling evidence to date that a donor stem cell transplant can improve survival rates for older patients with higher-risk myelodysplastic syndrome (MDS), Dana-Farber Cancer Institute investigators report at the virtual 62nd American Society of Hematology (ASH) Annual Meeting.

Despite being the only current cure for MDS and widely used for younger patients, transplant generally hasnt been offered to older patients because it has not been proven beneficial in that population. The new trial, conducted by the Blood and Marrow Transplant Clinical Trials Network, is likely to change that, according to study leaders. Involving 384 patients at 34 medical centers across the U.S., the trial found that transplantation of hematopoietic stem cells from compatible donors nearly doubled the survival rate of patients age 50-75.

Transplantation has been underutilized, historically, in this patient group, said study senior author Corey Cutler, MD, MPH, FRCPC, of Dana-Farber. Based on our findings all patients should at least be referred to a transplant center so that those who are eligible and have a suitable donor can undergo transplant and have better survival. It is important to refer these patients early so the transplant center can work on finding an optimal donor right from the get-go.

MDS encompasses a group of disorders in which blood-forming cells in the bone marrow become abnormal, resulting in the production of defective blood cells. In about one in three patients, MDS can progress to acute myeloid leukemia, a rapidly growing cancer of bone marrow cells.

Allogeneic hematopoietic stem cell transplantation replaces a patients abnormal blood-forming stem cells with healthy ones from a compatible donor. Because the procedure hadnt been proven to be helpful for older patients, it hasnt been covered by Medicare for people over age 65 unless done as part of an approved study. Medicare approved the design of the trial and is expected to consider the findings when determining future payment policies.

Participants in the new trial were referred to transplant centers, which searched for suitable stem cell donors. The 260 patients who were matched with a donor within 90 days were assigned to receive a stem cell transplant; the other 124 patients received standard supportive care.

Roughly three years after enrolling in the trial, 47.9% of those slated for transplant were alive, compared to 26.6% of those for whom no donor had been found at the 90-day mark. Survival without a recurrence of leukemia was also higher in those assigned to receive a transplant (35.8%) than in those who were not (20.6%). The researchers observed no significant differences among subgroups and no differences in quality of life between the two study arms.

Cutlerpresented findings on this study at the Whats on the Horizon: Practice-Changing Clinical Trials press briefing on Friday, Dec. 4 at 12:30 p.m. EST. Further details were presented during Session 732, Abstract 75, on Saturday, Dec. 5 at 10:30 a.m. EST.

Cutlers disclosures include a consulting or advisory role for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte.

Complete details on Dana-Farbers activities at ASH are available online at http://www.dana-farber.org/ash.

This press releasewas originally published on December 4, 2020, by Dana-Farber Cancer Institute. It is republished with permission.

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Donor Stem Cell Transplant Improves Survival in Older Patients with Myelodysplastic Syndrome - Cancer Health Treatment News

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By Staff Reporter 7m ago

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CAPE TOWN - International cricketer JP Duminy has his sights set on raising R400 000 in conjunction with the South African Bone Marrow Registry (SABMR) the figure thats still needed this year for them to match donors with patients suffering from life-threatening blood disorders who cant afford it.

Alicia Venter, Head of Patient Services at the SABMR says for many who dont have medical aid, the costs associated with finding a donor are a barrier to getting the life-saving treatment they need.

These costs include the search for an unrelated donor match in cases where no suitably matched donors are found among family members, testing and verification, the procurement and transportation of stem cells (from anywhere in the world), as well as travel and accommodation of the donor should the collection centre be far from home. Costs related to bone marrow stem cell transplants from international donors are more than double that of local donors.

Our Patient Assistance Programme is available to patients who are unable to obtain adequate funds for the treatment or in cases where their medical aid doesnt cover donor searches, despite appeal, explains Venter.

The SABMRs Give a Little Save a Life campaign, which kicks off on 10 December is being steered by Duminy, who is a long-time ambassador for the registry.

The Covid-19 pandemic has resulted in all the SABMRs events being cancelled, which usually brings in the bulk of the funds annually for the Patient Assistance Programme.

Right now, there are two young South Africans awaiting bone marrow stem cell transplants, whose families cant afford the cost of finding a donor.

One is a 6-year-old boy from Gauteng who has been diagnosed with Acute Lymphocytic Leukaemia and the other a 19-year-old girl from the Free State who has Acute Myeloid Leukaemia.

Their only hope of survival is a stem cell transplant. By rallying together, we can raise the funds to make it a reality and give them the second chance they deserve. In my life, Ive experienced many exhilarating moments both on and off the field and wish the same for these two young patients and others who are in a similar position. If you have the means to give, even if its just R50, youll never regret it.

At any given time, there are more than 200 patients in SA that need a bone marrow transplant unfortunately, many of whom cant afford it. While its been a tough year with very little funding coming in, the SABMR managed to redirect funds from its own reserves toward the programme.

This has helped to cover some of the key costs associated with finding suitably matched unrelated donors for eight patients.

Kamiel Singh, Head of Sustainability at the SABMR says while this years Give a Little Save a Life campaign will be solely online, he hopes it will galvanise a new generation of social media-savvy fundraisers that will support the SABMRs efforts.

Social media enables people to engage with each other and healthcare in ways that were almost unimaginable a decade ago. By combining the power of social media and sporting heroes such as JP Duminy, we hope to raise enough funds to make a real difference to the lives of hundreds of patients suffering from blood disorders in the coming year, says Singh.

Donations toward the registrys Patient Assistance Programme can be made via:

https://www.backabuddy.co.za/sabmrgivealittle and http://www.sabmr.co.za where there are various payment options available.

The SABMRs Give a Little Save a Life campaign can be followed on the following social media platforms: Facebook Twitter and Instagram

@IOLSport

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JP Duminy goes to bat for the SA Bone Marrow Registry - IOL

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DUARTE, Calif.--(BUSINESS WIRE)--City of Hope doctors participated in research presented at the American Society of Hematology (ASH) virtual meeting, Dec. 5 to 8, that are helping advance the treatment of blood cancers, including one study which demonstrated allogeneic stem cell transplants do have a survival benefit for older adults with myelodysplastic syndromes (MDS) compared with current standard of care.

The study is the largest and most definitive trial to demonstrate the benefits of an allogeneic stem cell transplantation for older adults with MDS, and is just one of numerous studies that City of Hope doctors help lead with the aim of finding more effective treatments of various blood cancers.

This years ASH conference truly showcases City of Hopes leadership in finding more effective treatments for blood cancers, said Stephen J. Forman, M.D., director of City of Hopes Hematologic Malignancies Research Institute. Whether its finding innovative treatments to make it possible for more older adults with cancer to receive stem cell transplants, or pursuing therapies that are more effective with fewer side effects, City of Hope doctors continue to lead innovative research in blood cancers and other hematological malignancies.

City of Hope doctors are leading novel clinical trials for patients with leukemia, lymphoma and other blood cancers.

Multicenter clinical trial led by City of Hope makes stem cell transplant possible for older adults with myelodysplastic syndromes

Allogeneic hematopoietic cell transplantation, or stem cell/bone marrow transplants, for blood cancers that have recurred or are difficult to treat can put the disease into long-term remission and provide a potential cure. The therapy establishes a new, disease-free blood and immune system by transplanting healthy blood stem cells from a donor into a cancer patient after destroying the patients unhealthy bone marrow.

City of Hope and other institutions started this therapy in 1976, primarily for younger patients with blood cancers. The therapy involves using high-dose chemotherapy and/or radiotherapy to make room for a person to receive new stem cells; serious side effects can also occur after transplant. Because of these and other considerations, for many years, older adults with blood cancers have not been considered for transplants.

City of Hope has been leading the way to make transplants possible for more older adults with various cancers.

A new study presented at ASH demonstrates transplants are now a possibility and beneficial for patients with myelodysplastic syndromes (MDS). Approximately 13,000 people in the United States each year are diagnosed with MDS, an umbrella term describing several blood disorders that begin in the bone marrow.

Co-led by City of Hopes Ryotaro Nakamura, M.D., director of City of Hopes Center for Stem Cell Transplantation, the study is the largest and first trial to demonstrate the benefits of an allogeneic stem cell transplantation for older adults with MDS as opposed to the standard of care currently provided to these patients. The multicenter trial for patients aged 50 to 75 with serious MDS compared how long transplant patients survived with those who didnt receive a transplant, as well as disease progression and quality of life. The transplant therapy used reduced-intensity conditioning, which delivers less chemotherapy and radiation before transplant and relies more on the anti-tumor effects of the therapy.

Between 2014 and 2018, the study enrolled 384 participants at 34 cancer centers nationwide. It included 260 patients who were able to find a donor for a transplant, as well as 124 patients who did not find a donor for a transplant.

After three years, nearly 48% of MDS patients who found a donor for transplant had survived compared with about 27% of those patients who didnt have a donor for transplant and received current hypomethylating therapy, a type of chemotherapy that is current standard of care for MDS. Leukemia-free survival which is relevant because myelodysplastic syndrome can develop into leukemia was also greater in transplant recipients after three years nearly 36% compared with about 21% for those who did not have a transplant.

There was a large and significant improvement in survival for patients who had a transplant, Nakamura said. The benefit margin in overall survival was over 20% (21.3%) for patients who had a transplant.

In addition, quality of life was the same for both transplant and nontransplant patients. There were no clinically significant differences when taking such measurements as physical and mental competency scores.

This is an extremely exciting study because it provides evidence that stem cell transplant is highly beneficial for older patients with serious MDS and will likely be practice-changing for this group, Nakamura said. Before, many doctors wouldnt even consider a transplant for this group of patients, but our study demonstrates that these patients should be evaluated for a transplant, which could potentially provide a cure for their disease.

The trial is part of Blood and Marrow Transplant Clinical Trials Network, which was established with support from the National Heart, Lung, and Blood Institute and National Cancer Institute, because of a critical need for multi-institutional clinical trials focused directly on improving survival for patients undergoing hematopoietic cell transplantation.

Updated results from a study of a potential new CAR T cell therapy, liso-cel, for relapsed/refractory chronic lymphocytic leukemia

Patients with relapsed or difficult-to-treat chronic lymphocytic leukemia/small lymphocytic leukemia continue to do well 24 months after receiving lisocabtagene maraleucel (liso-cel) chimeric antigen receptor (CAR) T cells, according to Tanya Siddiqi, M.D., director of City of Hopes Chronic Lymphocytic Leukemia (CLL) Program, which is part of the Toni Stephenson Lymphoma Center. She presented these findings during the 2020 ASH annual meeting virtual conference.

Overall, 23 and 22 patients were evaluated for safety and efficacy in this phase 1 trial, respectively. Their median age was 66 and they had received a median of four prior therapies; all patients had received prior ibrutinib, which is one of the standard of care drugs for CLL.

The overall response rate, or patients whose CLL diminished after liso-cel CAR T cell therapy, was 82%, and 45% of patients also had complete responses, or remissions.

After 15 months of treatment, 53% of patients maintained their responses to the therapy, and six patients continued to be in remission. After 18 months, 50% of patients maintained their response, and there were five remissions. All seven patients who completed the 24-month study maintained their response. Median progression-free survival, or the amount of time the cancer did not worsen during and after treatment, was 18 months.

As early as 30 days after receiving liso-cel, about 75% of 20 patients evaluated for the therapys efficacy had undetectable minimal residual disease (MRD, or no detectable traces of cancer) in the blood and 65% had undetectable MRD in the marrow.

These are remarkable results for a group of patients that prior to this CAR T treatment had no good treatment options if they had already progressed on novel targeted therapies like ibrutinib and venetoclax, Siddiqi said. Liso-cel is providing new hope for CLL patients, and the remissions are also long lasting with few serious side effects.

Because of its safety and effectiveness in clinical trials, liso-cel, which targets the CD19 protein on cancer cells, may soon receive approval from the Food and Drug Administration as a commercial therapy for relapsed or refractory B cell lymphoma. City of Hope is also taking part in the phase 2 trial of liso-cel in CLL patients.

Consolidation treatment with brentuximab vedotin/nivolumab after auto stem cell transplant for relapsed/refractory Hodgkin lymphoma patients leads to 18-month progression free-survival

Patients who have Hodgkin lymphoma that has not been cured by initial treatment will usually receive more chemotherapy and an autologous hematopoietic cell transplant. But even after a stem cell transplant, recurrence of the lymphoma is possible.

This multicenter phase 2 clinical trial, led by City of Hope, examined whether treating patients with brentuximab vedotin (BV), an antibody-based treatment that targets delivery of chemotherapy only to Hodgkin lymphoma cells, and nivolumab, which works by blocking the PD-1 immune checkpoint pathway that Hodgkin lymphoma hijacks to evade the immune system, was safe and effective as consolidation to prevent disease recurrence after transplant in patients with high-risk Hodgkin lymphoma.

Alex Herrera, M.D., assistant professor in City of Hope's Department of Hematology & Hematopoietic Cell Transplantation, discussed 19-month progression-free survival for trial participants, as well as overall survival, safety and response rates during ASH.

Fifty-nine patients were enrolled in the trial. Patients received the consolidation treatment starting a median of 54 days after transplant, and received a median of eight cycles of the therapy. The 19-month progression-free survival in patients was 92%, and overall survival in patients was 98%. Only three patients relapsed after receiving BV and nivolumab consolidation after transplant, and one patient passed away due to PCP pneumonia unrelated to the study treatment.

The most common sides effects related to the treatment were peripheral neuropathy (51%), neutropenia (42%), fatigue (37%) and diarrhea (29%).

Using brentuximab vedotin and nivolumab after transplant is a promising approach for preventing relapse of Hodgkin lymphoma after transplant that merits further study, Herrera said.

City of Hope doctors published research on innovative approaches against graft-versus-host-disease

Historically, a bone marrow/stem cell transplant is more likely to be effective if patients have a donor who is a 100% match, or as close to that as possible. Finding that perfect match is more difficult for African Americans, Latinos, Asian Americans and other ethnic groups as bone marrow donor registries are still trying to increase the number of non-white donors.

Transplant doctors are also looking for ways to make the transplant more effective if a perfect match cant be found; donors who are not a 100% or close match are referred to as mismatched unrelated. One major barrier to these transplants being effective is a condition known as graft-versus-host-disease (GVHD). The condition, which is more common in transplants involving mismatched donors, is caused by donated cells that recognize the recipient's cells as foreign and attack them, damaging the skin, eyes, lungs, liver and digestive tract.

In order to help prevent GVHD, therapies can be given to patients after transplant. A prospective clinical trial at City of Hope examined whether using cyclophosphamide after an infusion of stem cells could prevent GVHD.

Thirty-eight patients were enrolled in the trial, which is the first to examine the use of cyclophosphamide in transplants with a mismatched unrelated donor.

With a median follow-up period of 18 months, 87% of patients had survived, and the majority did not relapse or develop severe GVHD.

During the first 100 days post-transplant, acute GVHD incidence was around 50%; most cases were mild to moderate while severe GVHD was only 15%. A year after transplant, 52% of patients had some form of chronic GVHD, but only 3% had moderate or severe chronic GVHD.

The trial also examined toxicities, infections and immune system recovery after the transplant.

Our study showed that patients who received a transplant from a mismatched unrelated donor using post-transplant cyclophosphamide had a comparable outcome to what we see in matched donor transplants with few cases of serious GVHD cases, said Monzr Al Malki, M.D., associate clinical professor of City of Hopes Department of Hematology & Hematopoietic Cell Transplantation and director of unrelated donor BMT and haploidentical transplant programs. Our data support further development of this therapy in transplant patients who would otherwise have no suitable donors and limited treatment options.

City of Hopes Anthony Stein, M.D., also led a pilot trial that examined whether a new treatment approach may reduce the rate of GVHD in patients with acute myelogenous leukemia (AML) who have received an allogeneic hematopoietic cell transplant. Although a transplant can put AML into remission, GVHD remains the main serious complication after transplant, impacting a patients quality of life and increasing health care costs.

Eighteen patients between the ages of 18 and 60 enrolled in the trial. Each patient received a novel conditioning regimen of total marrow and lymphoid irradiation, which targets a patients marrow and lymph nodes while reducing radiation to other parts of the body, and cyclophosphamide, a therapy that suppresses the immune system. Tacrolimus was also provided to patients.

Radiation was delivered twice daily on the fourth day before transplant and on the day of transplant without chemotherapy. Cyclophosphamide was given to patients on the third and fourth day after transplant.

There were mild to moderate toxicities. Acute GVHD developed in two patients and only one patient developed the most serious GVHD. Five patients developed mild chronic GVHD. Nearly 60% of patients had not developed GVHD or the condition had not worsened after a year.

After a year, all patients had survived, and 83% had not relapsed. After two years, nearly 86% of patients had survived, and the relapse number remained the same.

The therapeutic approach did not interfere with the transplant process as all patients engrafted, or the donors cells started to produce bone marrow and immune cells.

This is welcome news for AML patients who receive an allogeneic transplant and are concerned about developing GVHD, said Stein, associate director of City of Hope's Gehr Family Center for Leukemia Research. Our study demonstrated that using this new combination of therapies is safe and feasible and does not interfere with the engraftment process.

In addition, after a year, patients in this trial were no longer taking immunosuppressive therapy and had an improved quality of life, Stein said. He added that because many of the patients didnt have GVHD, health care costs after a year were also lower than if patients required treatment for the condition.

City of Hope now plans to start a larger phase 2 trial using this treatment approach.

Bispecific antibodies continue to show promise against blood cancers

Mosunetuzumab is a promising new immunotherapy for the treatment of relapsed/refractory non-Hodgkin lymphoma (NHL) that recently received breakthrough therapy designation from the Food and Drug Administration. The designation is intended to expedite the development and review of drugs for serious or life-threatening diseases.

Elizabeth Budde, M.D., Ph.D., assistant professor in City of Hope's Department of Hematology & Hematopoietic Cell Transplantation, is leading clinical trials that are showing how well mosunetuzumab works against NHL. At this years ASH, one trial discussed is how the therapy is working for patients with follicular lymphoma.

Mosunetuzumab is a bispecific antibody targeting both CD3 (a protein found on the surface on T cells) and CD20 on the surface of B cells. The therapy redirects T cells to engage and eliminate malignant B cells.

Sixty-two patients, ranging in age from 27 to 85 years old, were enrolled in the trial for follicular lymphoma. They received intravenous doses of mosunetuzumab.

Sixty-eight percent of the patients responded to the therapy, and 50% had a complete response, or went into remission. Consistent complete response rates occurred even in patients with double refractory disease and patients who received prior CAR T cell therapy. Median duration of response was approximately 20 months, and media progression free survival was nearly one year.

Side effects were reported in 60 patients with serious adverse effects in 22 patients. The most frequently reported serious side effects were hypophosphatemia, an electrolyte disorder, and neutropenia, a condition caused by low numbers of white blood cells. Fourteen patients experienced cytokine release syndrome, but none required extensive treatment for it.

Neurological side effects included headache, insomnia and dizziness.

Patients in this trial had high response rates and their disease remained in control for a year, Budde said. This is remarkable because many patients were no longer responding to other therapies.

About City of Hope

City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hopes translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope has been ranked among the nations Best Hospitals in cancer by U.S. News & World Report for 14 consecutive years. Its main campus is located near Los Angeles, with additional locations throughout Southern California. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.

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City of Hope Doctors Present Innovative Therapies to Better Treat Blood Cancers at American Society of Hematology Virtual Conference - Business Wire

Recommendation and review posted by Bethany Smith

REDWOOD CITY, Calif.--(BUSINESS WIRE)--Jasper Therapeutics, Inc., a biotechnology company focused on hematopoietic cell transplant therapies, today announced clinical data from its ongoing multicenter Phase 1 clinical trial of JSP191, a first-in-class anti-CD117 monoclonal antibody, in patients with severe combined immune deficiency (SCID). The trial is evaluating JSP191 as a conditioning agent to enable stem cell transplantation in patients with SCID who are either transplant-naive or who received a prior stem cell transplant with a poor outcome.

Data from the first transplant-nave SCID patient in the Phase 1 trial, a 6-month-old infant, showed that a single dose of JSP191 administered prior to stem cell transplant was effective in establishing sustained donor chimerism followed by development of B, T and NK immune cells. No treatment-related adverse events were reported. The data were presented by primary investigator Rajni Agrawal-Hashmi, M.D., of Stanford University, at the 62nd American Society of Hematology (ASH) Annual Meeting & Exposition.

We have previously shown that JSP191 can be successfully used as a single conditioning agent in SCID patients who had failed a previous transplant, said Kevin N. Heller, M.D., Executive Vice President, Research and Development, of Jasper Therapeutics. This new data presented at ASH 2020 showing success in an infant with SCID undergoing a first transplant provides proof of concept of the safety and efficacy of the use of JSP191 as an alternative to genotoxic chemotherapies currently used to deplete stem cells prior to transplant.

Hematopoietic cell transplantation offers the only curative therapy for SCID, a severe genetic immune disorder that leaves patients without a functioning immune system. With this approach, standard-of-care chemotherapeutic conditioning regimens are given prior to transplant to reduce the number of blood stem cells in the bone marrow to make space for donor blood stem cells to engraft and cure the patient. JSP191 is designed to replace the need for chemotherapeutic conditioning agents, which are DNA-damaging and highly toxic.

Dr. Heller added, With our Phase 1 trials in SCID and hematologic disorders underway, we are planning to expand the development of JSP191 into additional indications, such as gene therapies, autoimmune diseases, Fanconis anemia and other rare disorders that can be cured by stem cell transplant.

The open-label, multicenter Phase 1 study is evaluating the safety, tolerability and efficacy of JSP191 as a conditioning agent in patients with SCID undergoing first or repeat hematopoietic cell transplantation. Up to three different doses of JSP191 are being assessed for dose-limiting toxicities. The trial is currently open for enrollment at Stanford University, the University of California, San Francisco, Memorial Sloan Kettering Cancer Center, the University of California, Los Angeles, and Cincinnati Childrens Hospital. Additional clinical trial sites in the United States will initiate enrollment in the coming weeks.

About SCID

Severe combined immune deficiency (SCID) is a group of rare disorders caused by mutations in genes involved in the development and function of infection-fighting immune cells. Infants with SCID appear healthy at birth but are highly susceptible to severe infections. The condition is fatal, usually within the first year or two of life, unless infants receive immune-restoring treatments, such as transplants of blood-forming stem cells, gene therapy or enzyme therapy.

About JSP191

JSP191 (formerly AMG 191) is a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow. JSP191 binds to human CD117, a receptor for stem cell factor (SCF) that is expressed on the surface of hematopoietic stem and progenitor cells. The interaction of SCF and CD117 is required for stem cells to survive. JSP191 blocks SCF from binding to CD117 and disrupts critical survival signals, causing the stem cells to undergo cell death and creating an empty space in the bone marrow for donor or gene-corrected transplanted stem cells to engraft.

Preclinical studies have shown that JSP191 as a single agent safely depletes normal and diseased hematopoietic stem cells, including in animal models of SCID, myelodysplastic syndromes (MDS) and sickle cell disease (SCD). Treatment with JSP191 creates the space needed for transplanted normal donor or gene-corrected hematopoietic stem cells to successfully engraft in the host bone marrow. To date, JSP191 has been evaluated in more than 90 healthy volunteers and patients.

JSP191 is currently being evaluated as a sole conditioning agent in a Phase 1/2 dose-escalation and expansion trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplant for severe combined immunodeficiency (SCID), which is potentially curable only by this type of treatment. JSP191 is also being evaluated in a Phase 1 study in patients with MDS or acute myeloid leukemia (AML) who are receiving hematopoietic cell transplant. For more information about the design of these clinical trials, visit http://www.clinicaltrials.gov (NCT02963064 and NCT04429191). Additional studies are planned to advance JSP191 as a conditioning agent for patients with other rare and ultra-rare monogenic disorders and autoimmune diseases.

About Jasper Therapeutics

Jasper Therapeutics is a biotechnology company focused on the development of novel curative therapies based on the biology of the hematopoietic stem cell. The companys lead compound, JSP191, is in clinical development as a conditioning antibody that clears hematopoietic stem cells from bone marrow in patients undergoing a hematopoietic cell transplant. This first-in-class conditioning antibody is designed to enable safer and more effective curative hematopoietic cell transplants and gene therapies. For more information, please visit us at jaspertherapeutics.com.

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Jasper Therapeutics Announces Data from First Transplant-naive Patient in Phase 1 Clinical Trial of JSP191 as Conditioning Agent in Patients with SCID...

Recommendation and review posted by Bethany Smith

A FORMER hairdresser from Bournemouth is appealing for people to help raise money to have life-saving surgery in Mexico to get rid of her Multiple Sclerosis once and for all.

Having been admitted to Royal Bournemouth Hospital for a suspected stroke or brain tumour in March 2017, at the age of 47, Kirsten Hannibal was found to have multiple lesions on her brain and was diagnosed with CIS which later progressed to MS.

During lockdown, Kirsten has researched into different ways to stop Multiple Sclerosis dead in its tracks, one of them being Hematopoietic Stem Cell Transplantation.

Although the procedure, which involves the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, is not widely accessible in the UK, it is available in Mexico, considered a world class hub for HSCT.

However she must raise over 40,000 to cover flights to Mexico as well as the cost of the procedure.

Vicky Dixon has set up a crowdfunding page to raise money for Kirstens medical procedure.

In a statement written on her crowdfunding page, she said: Our family are joining forces to raise the money needed to send our Kirsten to Mexico for Hematopoietic Stem Cell Transplantation treatment that is not universally available on the NHS, but will hopefully give Kirsten a chance of a future; a life free of pain, disability and heart breaking challenges.

We hope that Kirsten can follow the footsteps of other British MS sufferers and go to Mexico, a world class centre for HSCT, and cheaper than the UK, at the cost of 43,500.

The first large, randomised control trial, and several meta-analyses of HSCT, have confirmed that HSCT is a very effective therapy. This is now tipping the scales for HSCT becoming a mainstream treatment for MS in Britain.

However, the treatment has to take place before the MS becomes too advanced, and as it will be years before HSCT might be offered more widely, Kirsten would by then be swallowed up by the MS and not a suitable candidate for treatment.

Kirsten is on the brink of becoming too disabled for this treatment, hence the urgency of our appeal.

Sadly, the 46-year-old is now travelling a path similar to one her family have walked before.

In 1984 her mother at the age of 32 was diagnosed with lymphoblastic leukaemia and the Echo covered the story.

Her mother underwent aggressive chemotherapy and was the receiver of a ground-breaking treatment with a bone marrow transplant.

She was the first patient to receive this treatment in the south and, whilst the treatment was deemed a success, sadly her mother died.

Lynda Smiths legacy lives on because her bravery in allowing this treatment to take place is now the lifeline to many children and adults alike who survive leukaemia.

The treatment Kirsten is looking to have is similar to her mothers treatment, except it would be her own bone marrow that would be harvested. She will then be given chemotherapy and then the day Kirsten longs for, freedom from the disease.

The new birthday she dreams of is a stem cell birthday celebrated when the bone marrow is put back into her body giving her the chance of stopping Multiple Sclerosis.

So far, Kirstens fundraising appeal has raised 4,535, just over 10 per cent of her target.

To donate, visit https://www.gofundme.com/f/multiple-sclerosis-and-an-urgent-bid-for-freedom?utm_source=customer&utm_medium=email&utm_campaign=p_cp+sharesheet.

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Bid to fund stem cell treatment in Mexico for woman with MS - Bournemouth Echo

Recommendation and review posted by Bethany Smith

Cell therapies involve the transfer of live cells into a patient to help treat, prevent or potentially cure diseases. One category of cell therapy focuses specifically on the use of stem cells, or cells within the body that have the potential to replace those that are lost through injury or disease. Their versatility and ability to transform allow them to replace problematic or deactivated cells with new, healthy ones is giving patients around the world a second chance at life.Stem cells are found all throughout the human bodyincluding the skin, muscle tissue and even deep inside bone marrow.

Bone marrow, the spongy substance that fills the inner cavities of our bones, is a rich source ofhematopoietic stem cells. These cells are particularly valuable for their ability to develop into all types of blood cells, including white blood cells, red blood cells and platelets. Due to their unique ability,hematopoietic cells can be used to treat certain types of cancer, such as leukemia and lymphomaand have become a staple in the field of regenerative medicine.

Bone marrow aspirate concentrate(BMAC) is a procedure that collects bone marrow from a patient's body and then concentrates it to create the optimal level of stem cells and other crucial growth factors, which can offer a variety of health benefits that traditional surgical methods simply can't offer. Stem cells and their descendants, known as progenitor cells, combined with other bone marrow cells and platelets, have the potential to restore function when injected directly into the patient's damaged tissue. The BMAC procedure is popularly used by physicians who practice orthopedic surgery, pain management and sports medicine. It has been shown torepair tissue damage, preserving function and strengthand in some cases has even beenused as an alternative for more intensive procedures such as joint and hip replacements.

Bone Marrow Aspirate Concentrate is currently being used to:

While there are many bone marrow concentrate technologies currently out on the market, there are none quite like theThermoGenesis PXPSystem. The PXPSystem is an automated, closed system designed for sterile bone marrow separation and concentration. The automated system utilizes highly sensitive sensors to reduce the amount of red blood cells (RBCs) from the initial bone marrow aspirate, providing physicians with a high-quality final product.Red blood cell contaminationis, by far, the biggest issue physicians encounter when using open, non-automated bone marrow processing systems. When high RBC contamination occurs in the bone marrow concentrate, it can impair cell function and diminish the overall effectiveness of the cell treatments. The PXPSystem is specifically designed to eliminate RBCs contamination head-on, boasting aRBC reduction of over 99 percent.

[Link]

The PXPSystem obtains bone marrow concentrates easily, consistently, and reliably, setting itself apart from any other competitors on the market today. The automated nature of the system eliminates factors created by human error and allows for increased precision and control. It gives its user the ability to harvest a precise volume of cell concentrate from the bone marrow aspirate, while producing consistently high mononuclear cells (MNCs) and CD34+ progenitor cell recoveries.

[Link][Link]

Bone marrow aspirate is collected from the patient through a minimally invasive procedure, usually done under local or general anesthesia. After extraction, the aspirate is transferred into the PXP System and processed in a centrifuge to compartmentalize the aspirate into three separate chambers within the Disposable Cartridge - the central processing chamber, the red blood cell depletion chamber and the harvest chamber. The plasma, nucleated cells and RBCs are all sorted by density to create maximum separation of components. The RBCs are then removed and transferred to the depletion chamber, leaving users with a 6 ml harvest of enriched bone marrow concentrate (containing stem cells, platelets, growth factors) ready to be reintroduced into the patient.

The entire process only takes about twenty minutes from the moment the bone marrow aspirate is placed in the system to the point where it can be reinjected. For added convenience, the automated control module provides users with accurate data tracking and serves as a record for the entire process.

The PXPSystem is a tool for physicians looking for a quick, easy and efficient system for processing bone marrow. It is one of the most innovative systems available on the market and our mission is to make it even better. We are currently working with our partners in the field and evolving our products based on their feedback. Based on their response, we've begun designing a stripped-down version of the PXPSystem that requires less accessories and generates a smaller footprint, while still delivering a high-quality final product. Our applications are being developed with the needs of laboratories and physicians in mind, giving them the resources, they need to better serve their patients.

ThermoGenesis Holdings, Inc. (formerly Cesca Therapeutics Inc.), is a pioneer and market leader in the development and commercialization of automated cell processing technologies for the cell and gene therapy fields. We market a full suite of solutions for automated clinical biobanking, COVID-19 testing, point-of-care applications and large-scale cell processing and manufacturing with a special emphasis on the emerging CAR-T immunotherapy market. We are committed to making the world a healthier place by creating innovative solutions for those in need.

To see our full suiteof automated solutions,please visit the shop portion of our website today.

Disclaimer

Thermogenesis Holdings Inc. published this content on 08 December 2020 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 09 December 2020 18:24:01 UTC

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The Technology Behind Bone Marrow Cellular Processing: The PXP System - Marketscreener.com

Recommendation and review posted by Bethany Smith

CAMBRIDGE, Mass.--(BUSINESS WIRE)--HighPassBio, an ElevateBio portfolio company dedicated to advancing novel targeted T cell immunotherapies, today discussed the ongoing Phase 1 trial of the companys lead product candidate, an engineered T cell receptor (TCR) T cell therapy targeting HA-1 expressing cancer cells in an oral presentation at the 62nd American Society of Hematology (ASH) Annual Meeting. The Phase 1 clinical trial, which is being conducted by researchers at Fred Hutchinson Cancer Research Center, is designed to assess the feasibility, safety, and efficacy of this novel cell therapy in the treatment of leukemia following hematopoietic stem cell transplant (HSCT).

The prognosis for leukemia patients whove relapsed or who have residual disease following allogeneic hematopoietic stem cell transplantation is often poor, but we believe that by targeting the minor H antigen, HA-1, through a novel T cell immunotherapy, we can potentially treat and prevent subsequent relapse, said Elizabeth Krakow, M.D., MSc., Assistant Professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, principal investigator of the study, and presenting author. We have observed early promising indicators of anti-leukemic activity following treatment in this trial. We are eager to expand the trial to additional patients as we continue to research the feasibility, safety, and efficacy of this approach.

The abstract for the presentation titled Phase 1 Study of Adoptive Immunotherapy with HA-1-Specific CD8+ and CD4+ Memory T Cells for Children and Adults with Relapsed Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation (HCT): Trial in Progress, can be found on the ASH website under the abstract number 137726.

To date, four patients, including one pediatric patient, have received a total of six infusions in the Phase 1 clinical trial. Patient characteristic data was shared in the oral presentation at ASH, including documented HA-1 TCR T cell persistence in blood and bone marrow up to 18 months. In some patients, clear in vivo anti-leukemic activity was observed at the first dose level, including a subject with aggressive, highly refractory T-ALL and early post-HCT relapse. No significant toxicities attributed to the T cells have been observed, including no infusion reactions or evidence of cytokine release syndrome or graft versus host disease.

The Phase 1 clinical trial is currently recruiting adult and pediatric patients who have residual disease or relapsed leukemia or related conditions following HSCT. As part of the trial, transplant patients and prospective donors may be recruited to participate in the genetic screening portion to determine eligibility. More details are available on clinicaltrials.gov under the study ID number NCT03326921.

About TCR-Engineered T Cell Therapy

A key role of the immune system is to detect tumor antigens, engage T cells, and eradicate the tumor. However, the immune response to tumor antigens varies and is often insufficient to prevent tumor growth and relapse. An approach known as adoptive T cell therapy, using T cell receptors, or TCRs, can overcome some of the obstacles to establishing an effective immune response to fight off the target tumor. TCRs are molecules found on surface of T cells that can recognize tumor antigens that are degraded to small protein fragments inside tumor cells. Unlike CAR T cells that recognize only surface antigens, TCRs can recognize small protein fragments derived from intracellular and surface antigens offering a more diverse way to attack tumors. These small protein fragments show up on the tumor cell surface, with another protein called major histocompatibility complex (MHC), that are recognized by the TCRs and consequently signal the bodys immune system to respond to fight off and kill the tumor cells.

Tumor-specific TCRs can be identified and then engineered into T cells that recognize and attack various types of cancers, representing a novel approach to treating and potentially preventing disease.

Adoptive T cell therapy can be applied to tackling relapse of leukemia post hematopoietic stem cell transplant (HSCT) by targeting the antigens expressed only by the patients native cells, and not by the cells from the stem cell transplant donor. HA-1, a known minor histocompatibility antigen, is expressed predominantly or exclusively on hematopoietic cells, including leukemic cells. There is evidence that T cells specific for HA-1 can induce a potent and selective antileukemic effect. HA-1 TCR T cell therapy is a new investigational immunotherapy for the management of post transplantation leukemia relapse.

About Leukemia post HSCT Treatment and the Risk of Relapse

Leukemia, a cancer of the blood or bone marrow characterized by an abnormal proliferation of blood cells, is the tenth most common type of cancer in the U.S. with an estimated 60,140 new cases and 24,400 deaths in 2016. Leukemia arises from uncontrolled proliferation of a specific type of hematopoietic (blood) cell that is critical for a functional immune system. As a result, when patients are given very high doses of chemotherapy to eradicate leukemic cells, most normal cells are killed as well, necessitating a transplant of hematopoietic stem cells from a donor to reconstitute the patients bone marrow and circulating hematopoietic cells. In some cases, the transplanted T cells from the donor can also recognize and eliminate the hematopoietic cells, including leukemia, from the recipient, thus preventing relapse. This can be described as a graft versus leukemia effect. Other hematologic disorders related to leukemia, like myelodysplastic syndrome (MDS), can also be treated in this way.

While HSCT can be curative, it is estimated that 25-50 percent of HSCT recipients relapse; leukemia relapse remains the major cause of allogeneic HSCT failure, and the prognosis for patients with post-HCT relapse is poor. Relapse occurs following allogeneic HSCT in approximately one-third of patients with acute leukemia who undergo the procedure, and most patients subsequently die of their disease.

About HighPassBio

HighPassBio, an ElevateBio portfolio company, is working to advance a novel approach to treating hematological malignancies by leveraging T cell receptor (TCR)-engineered T cells, known as TCR T cells. The companys lead program is designed to treat or potentially prevent relapse of leukemia in patients who have undergone hematopoietic stem cell transplant (HSCT). The technology was born out of research conducted at Fred Hutchinson Cancer Research Center by world renowned expert, Dr. Marie Bleakley.

About ElevateBio

ElevateBio, LLC, is a Cambridge-based creator and operator of a portfolio of innovative cell and gene therapy companies. It begins with an environment where scientific inventors can transform their visions for cell and gene therapies into reality for patients with devastating and life-threatening diseases. Working with leading academic researchers, medical centers, and corporate partners, ElevateBios team of scientists, drug developers, and company builders are creating a portfolio of therapeutics companies that are changing the face of cell and gene therapy and regenerative medicine. Core to ElevateBios vision is BaseCamp, a centralized state-of-the-art innovation and manufacturing center, providing fully integrated capabilities, including basic and translational research, process development, clinical development, cGMP manufacturing, and regulatory affairs across multiple cell and gene therapy and regenerative medicine technology platforms. ElevateBio portfolio companies, as well as select strategic partners, are supported by ElevateBio BaseCamp in the advancement of novel cell and gene therapies.

ElevateBios investors include F2 Ventures, MPM Capital, EcoR1 Capital, Redmile Group, Samsara BioCapital, The Invus Group, Surveyor Capital (A Citadel company), EDBI, and Vertex Ventures.

ElevateBio is headquartered in Cambridge, Mass, with ElevateBio BaseCamp located in Waltham, Mass. For more information, please visit http://www.elevate.bio.

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ElevateBio's HighPassBio Presents on Novel T Cell Receptor Cell Therapy for Leukemia Relapse at 62nd Annual ASH Meeting - Business Wire

Recommendation and review posted by Bethany Smith

This weekend brought some really significant news in the long-running effort to use gene editing to treat human disease. As most readers will have heard, Boston Childrens Hospital and a Vertex/CRISPR effort both published papers in the NEJM addressing sickle-cell anemia and beta-thalassemia. (Update: edit to fix attribution).

These diseases have long been linked when it comes to gene therapy ideas, because both of them have defects in the hemoglobin protein as their cause. And its long been thought that both could be treated by getting adults to re-express the fetal hemoglobin protein its on a different gene entirely, and thus does not have any of the genetic problems that affect the adult hemoglobin gene. The normal course of events is for babies to stop expressing the fetal form and switch over to regular hemoglobin, and its been worked out that a particular transcription factor called BCL11a is a key player in that transcriptional repression of the fetal hemoglobin gene. That plays right into the usual way that we tend to think about therapeutic possibilities: whether its enzymes, receptors, or expression of whole proteins, we have a lot more tools to mess things up and interrupt processes than we have to make them run faster or better. So the possibility of interrupting BCL11as function has been a tempting one for many years.

Its hard to do by traditional means, though. (Full disclosure: I have, at different times in my career, been involved with such efforts, but none have ever come near the clinic.) Transcription factors are notoriously hard to get a handle on with small molecule therapeutics, and many unsuccessful runs have been taken at BCL11a ligands to try to interrupt its functions in one way or another. My general impression is that the protein doesnt much care about recognizing small-molecule ligands (and its far from the only one in that category, for sure). Youd think that if you ran a few hundred thousand (or a few million) various molecules past any given protein that youd find a few of them that bind to it, but that assumption is too optimistic for most transcription factors. Youre also going to have a hard row to hoe (to use an old Arkansas expression) if you try to break up their interactions with their DNA binding sites: a significant amount of capital has gone down the chute trying to get that to work, with (as far as I can tell) not much to show for it.

Theres another complication: BCL11a has a lot of other functions. Every protein has a lot of other functions, but for transcription factors, the issue can be especially fraught. If you had a small molecule that really did interfere with its activity, what would happen if you just took a stiff dose of it? Probably a number of things, including some interesting (and not necessarily welcome) surprises. There have been a number of ideas about how to get around this problem, but a problem it is.

So its on to biological mechanisms. The BCH team reports on using RNA interference to do the job they get cells to express a short hairpin RNA that shuts down production of BCL11a protein, with some microRNA work to target this to the right cell lines. And the Vertex/CRISPR team, naturally, uses CRISPR itself to go in and inactivate the BCL11a gene directly. Both approaches take (and have to take) a similar pathway, which is difficult and expensive, but still the best shot at such therapies that we have. You want the fetal hemoglobin expressed in red blood cells, naturally, and red blood cells come from CD34+ stem cells in the bone marrow. Even if you havent thought about this, you might see where its going: you take a bone marrow sample, isolate these cells, and then do your genetic manipulation to them ex vivo. Once youve got a population of appropriately re-engineered cells ready to go, you go kill off the bone marrow in the patient and put the reworked cells back in, so theyre the only source there for red blood cells at all. A bone marrow transplant, in other words a pretty grueling process, but definitely not as much as having some sort of blood-cell-driven cancer (where the therapy uses compatible donor cells from someone else without such a problem), or as much as having full-on sickle cell disease or tranfusion-dependent thalassemia.

You can also see how this is a perfect setup for gene therapy: theres a defined population of cells that you need to treat, which are available in a specific tissue via a well-worked-out procedure. The problem youre trying to correct is extremely well understood in fact, it was the first disease ever characterized (by Linus Pauling in 1949) as purely due to a genetic defect . And the patients own tissue is vulnerable to chemotherapy agents that will wipe out the existing cell population, in another well-worked-out protocol, giving the newly reworked cells an open landscape to expand in. You have the chance for a clean swap on a defined target, which is quite rare. In too many other cases the problem turns out to involve a fuzzy mass of genetic factors and environmental ones, none of which by themselves account for the disease symptoms, or the tissue doesnt allow you to isolate the defective cells easily or doesnt allow you to clear them out for any new ones you might generate, and so on.

Both the Vertex/CRISPR and BCH techniques seem to work and in fact, to work very well. There are now people walking around, many months after these treatments, who were severely ill but now appear to be cured. Thats not a word we get to use very often. They are producing enough fetal hemoglobin, more than enough to make their symptoms completely disappear no attacks, no transfusions, just normal life. And so far there have been no side effects due to the altered stem cells. An earlier strategy from Bluebird (involving addition of a gene for a modified adult hemoglobin) also seems to be holding up.

These are revolutionary proofs of concept, but at the same time, they are not going to change the course of these diseases in the world not right now, anyway. Bone marrow transfusion is of course a complex process that costs a great deal and can only be done in places with advanced medical facilities. But what weve established is that anything that can cause fetal hemoglobin to be expressed should indeed cure these diseases that idea has been de-risked. As has the general idea of doing such genetic alteration in defined adult tissues (either RNA interference or CRISPR). From here, we try to make these things easier, cheaper and more general, to come up with new ways of realizing these same goals now that we know that they do what we hoped that they would. This work is already underway new ways to target the affected cell populations rather than flat-out chemotherapy assault, new ways to deliver the genetically altered cells (or to produce them on site in the patients), ways to make the switchover between the two more gradual, and so on. There are lot of possible ways, and we now know where were going.

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Gene Therapy, Absolutely and For Real | In the Pipeline - Science Magazine

Recommendation and review posted by Bethany Smith

WASHINGTON, Dec. 8, 2020 /PRNewswire/ --Genetic mutations linked with cancer can occur during childhood or even before birth and proliferate in the body for many years before causing cancer symptoms, according to a new study. The study, which traced the genetic origins of a blood cancer in 10 individuals, suggests there may be untapped opportunities to detect cancer warning signs much earlier and potentially intervene to prevent or slow cancer development.

"Our preliminary findings show these cancer driver mutations were often acquired in childhood, many decades before the cancer diagnosis," said senior study authorJyoti Nangalia, MD,of the Wellcome Sanger Institute and University of Cambridge. "Our results finally answer the common question posed by patients, 'How long has this cancer been growing?' as we were able to study how these particular cancers developed over the entire lifetime of individual patients."

The researchers analyzed bone marrow and blood samples from 10 people with Philadelphia-negative myeloproliferative neoplasms, a type of cancer that causes stem cells in the bone marrow to produce too many blood cells. In the majority of patients, this cancer is driven by a genetic mutation called JAK2V617F. By assessing JAK2V617F, other cancer-linked mutations and hundreds of thousands of other mutations that a person naturally acquires throughout life, the researchers were able to trace the ancestry of different blood cells and estimate the time at which each patient acquired JAK2V617F and other important mutations.

They determined that, in these 10 patients, the first cancer-linked mutations emerged as early as a few weeks after the start of life and up to the first decade of childhood despite clinical disease presenting many decades later in life.

"We were not expecting this," said Dr. Nangalia. "In fact, in one patient, the JAK2 mutation was acquired more than 50 years before their diagnosis."

While it is often assumed that most cancers are diagnosed within a few years of their emergence, the findings point to a more gradual, lifelong process in which a single cell acquires a cancer-linked mutation early in life and then slowly grows over decades, ultimately leading to cancer.

"Some of these cancer-linked mutations are found in healthy individuals as we get older, suggesting that aging causes them," said Dr. Nangalia. "However, aging per se doesn't drive such growth it simply takes a long time for the clones to grow." Sometimes, the growing clones pick up additional cancer-linked mutations along the way, accelerating their growth, researchers found.

"For these patients, we calculated how many of these cancer clones would have been present in the past, and our results suggest that these clones may have been detectable up to 10 to 40 years before diagnosis," said Dr. Nangalia. "In addition to detecting the mutations, the rate at which the mutated clones grew was also very important in determining whether, and when, cancer develops." The findings suggest that genetic testing could help identify people at risk for cancer much earlier than current methods allow, according to researchers.

The next steps would be to understand the factors that influence the different rates of cancer growth and determine whether there could be ways to intervene and slow the growth of cells with cancer-linked mutations. The researchers say their method for pinpointing the origin of this blood cancer could also be applied to other mutations and other blood cancers. "Understanding the timelines of development of different cancers is critical for efforts aimed at early cancer detection and prevention," said Dr. Nangalia.

Jyoti Nangalia, MBBChir,Wellcome Sanger Institute and University of Cambridge, will present this study during the Late-Breaking Abstracts session on Tuesday, December 8 at 7:00 a.m. Pacific time on the ASH annual meeting virtual platform.

For the complete annual meeting program and abstracts, visit http://www.hematology.org/annual-meeting. Follow ASH and #ASH20 on Twitter, Instagram, LinkedIn, and Facebook for the most up-to-date information about the 2020 ASH Annual Meeting.

The American Society of Hematology (ASH) (www.hematology.org) is the world's largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 60 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. ASH publishes Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, and Blood Advances (www.bloodadvances.org), an online, peer-reviewed open-access journal.

SOURCE American Society of Hematology

http://www.hematology.org

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Researchers Trace the Origin of Blood Cancer to Early Childhood, Decades before Diagnosis - PRNewswire

Recommendation and review posted by Bethany Smith

What started out as a journey to better understand regulatory T cells has now led to an intriguing approach with an investigational cell therapy designed to prevent the risk of graft-versus-host disease (GVHD) and to improve relapse-free survival rates in patients undergoing hematopoietic stem cell transplantation (HSCT).

Data of a phase 1/2 trial recently showed that the first-generation precision cell treatment Orca-T compared with a historical control of standard HSCT demonstrated faster neutrophil (median, 12 days vs 14 days; P < .0001) and platelet engraftment (median, 11 days vs 17 days; P < .0001), decreased incidence of grade 2 or higher GVHD at 100 days (10% vs 30%, P = .005) and chronic GVHD at 1 year (3% vs 46%, P = .0002).1,2

The 1-year GVHD-free and GVHD relapse-free survival (GRFS) rates were 75% with the use of Orca-T vs 31% with standard HSCT (P < .0001). The comparator cohort was derived from contemporaneous patients who had been treated at Stanford University with a conventional allograft.

Along with feasibility of the approach, the results also highlight how Orca-T demonstrates potent anti-leukemic activity in patients who have active disease at HSCT, which suggests that the decrease of GVHD does not impact graft-vs-leukemia (GvL).

That is the most exciting part about the Orca-T story; it is the ability to do this with precision, with speed, and to export it to other sites. The results are intriguing, and very supportive, said Robert Negrin, a professor of medicine (blood and marrow transplantation), and chief of the Division of Blood and Marrow Transplantation at Stanford University.

In an interview with OncLive, Negrin, who is senior author on the trial, shared the evolution of Orca-T as a novel approach to HSCT, highlighted his robust experience with using this cell therapy at Stanford University, and how Orca-T is a potential prevention method for GVHD.

OncLive: Please provide some background to this therapeutic approach. What is the mechanism of action? How is it effective in patients undergoing transplant?

Negrin: This whole idea came from mouse studies many, many years ago, where we identified GVHD as being a dysregulated immune reaction that just keeps going, and going, and going. Like you and I, when we react to something, we have a reactionlet's say, influenza. Our body responds, and then we stop reacting and you get better. With GVHD, what we noticed in using a bioluminescent animal model is that the alloreactive T cells just keep going, going, and going and are unrelenting in mice, just like in people. The problem is very similar and affects certain organs in a very similar way.

Therefore, we went about trying to understand the use of so-called regulatory cells. These are cells that everybody has that help control immune reactions. We just applied them in this clinical scenario, first in mice work done by Matthias Edinger, MD, when he was a postdoctoral fellow many years ago [and other researchers]. All of them were very actively involved in these studies, and showed, somewhat surprisingly, that the administration of regulatory T cells could control this dysregulated immune response that we called GVHD.

Probably more surprising was that, at least in the animal models, it also allowed for the benefits of transplant, namely, the graft-vs-tumor effect and better immune recovery. This was in large part because GVHD also impacts the immune repertoire and where the immunity is developed in the recipient.

All of this was very nice in mouse models and was very elegant. We did a lot of studies, published a number of nice papers, and thought this would be a great idea because it sort of solved, or at least addressed, the principal problems after bone marrow transplantationnamely, avoidance of GVHD yet retention of graft-versus-tumor effects and better immunity. A lot of times, people say, "Oh, that sounds good in mice, but, that's too good to be true." And, theyll ask, "Will that all work in people?"

Where did the biggest challenges lie in this approach?

The big challenge came about to try to apply this to patients. We also have one other interesting point that is relevant. If we gave the regulatory T cells first, before the so-called conventional CD4+/CD8+ cells, that allowed for a lower dose of regulatory T cells. This is because a big challenge is the paucity of these cells; you and I don't have that many.

Then, the other big challenge was the technical ability to isolate in cells. What we do in mice is cell sorting, which is a standard technology. But, that was not developed in people because we're bigthere are a lot of cells, and cell sorting is rather slow, and it's very specific. To get enough cells takes a really long time. It's somewhat of a heroic thing to do in people, to get the adequate amount ourselves; of course, we don't really know what this proper cell dose is.

However, what we thought we learned was that the ratio of conventional to regulatory T cells was the key component. Also, if you give the regulatory T cells first, you can get fewer numbers. Those are things you can do in transplant. You can get the cell from the donor, and you can give cells in a certain sequence; all of those things are very doable. It seemed like an attractive thing to do in patients.

Then, the question was: Does it work? There are 3 groups that have really pioneered this work. The first study came from the University of Perugia in Italy. They did this in haploidentical transplantation; you cannot avoid immunosuppression in haploidentical transplants. They were able to show in several nice papers that you could do this strategy, and seemingly, get away with low risk of GVHD, and also low relapse. This is because the other issue is: how do you measure the graft-vs-tumor effect? There is no assay, and we have no test; you have to wait and see who relapses and who doesn't. Therefore, they also showed rather convincingly that you could reduce GVHD risk, yet, there was a very low risk of relapse in their high-risk patient population. Those were very important [data].

Another study from the University of Minnesota did this with umbilical cord blood. They expanded the regulatory T cells from a third cord blood unit, which is somewhat heroicit is another level of complexity to isolate the cells and then expand them. We did this in matched donorseither matched siblings or matched unrelated donors. We published a paper in JCI Insight several years ago showing the initial results, and they look quite favorable.

Therefore, what I think is most exciting about what Orca Bio has done is they are developing technology to isolate the cells more quickly, to be able to do this on a clinical scale, with precision, and with speed. Also, [they are developing the technology] to be able to distribute it to anybody, because the criticism of all these studies is that, "Oh, that's nice. But, this is a single-institution study. Is this really true? Can this be exported? Could this be something that [an organization] other than these [individual] centers are really focused in this area and have developed these technologies could really do? Orca Bio is developing the technology, and improving the technology, because it's still very cumbersome, and exporting the technology so that you could do this, theoretically, at any center.

That's what I think is most exciting about the Orca Bio abstract; it is demonstrating that this can be done. It certainly opens the door to prevention of GVHD. As we move into an era of using cell-based therapeutics, now, this opens up many other possibilities, because you use these regulatory cells and autoimmune disorders and organ transplant tolerance. There are many other cell types that have potential clinical utility, but getting them, and purifying them, is a big challenge. There are many other possibilities that one could think of.

Obviously, more time will be required to follow these patients, but they certainly are supportive of the idea that you can improve overall outcomes using this strategy. That's what we hope to be able to demonstrate further.

Please focus on the scalability of this approach. Through these types of collaborations, how do you see Orca-T potentially moving through the FDA pipeline?

In academia, we don't develop drugs. It's too much, we don't have the resources, we don't have the capability, and we don't have the monitoring capability that is required for multi-institutional studies. Where these commercial partners come in is, they can raise money for interesting concepts, which Orca Bio has done, and they can export this to other centers, and that's critically important.

As we've seen in the CAR T-cell [therapy] world, that can be a quite successful commercial business. Also going through the process of an FDA approvalwhich Orca Bio is moving along in that processand getting the right designations is critically important to commercial entities. In academia, it's important to us, but that's just not our focus.

We don't have the resources around, the people and the expertise to really drive things through that process. We're good at developing the studies and getting FDA approvals, and [investigational new drug applications], but not really [good at] developing drugs as a commercial entity. This collaboration is key to doing this successfully; for example, at Orca Bio, [they have] technology to separate cells more efficiently and effectively. They also have the resources to do a multi-institutional clinical trial, and the expertise to move something through and present it to the FDA. Those are key components.

Could you expand on the study and respective data from this phase 1/2 trial?

Here at Stanford Cancer Institute, we did find in our patients that giving low doses of immunosuppressive medications with a single agent seem to improve the outcomes, and it's remarkable how well these patients have gone through the transplant. It's a little bit hard to appreciate an abstract until you take care of these patients, and many of them just sort of move to the transplant with relatively little challenges. We have not seen greater risks of things like infection [or] disease recurrence; those are obviously things that will be followed.

When we look at the 1-year GVHD relapse-free survival rate, which is an endpoint that most transplant studies would agree is the most important end point, the overall outcomes are much more favorable compared with a historical control group.

The data are very encouraging, and the overall outcomes look very strong in a reasonable number of patients now. We think it's important for the community to hear about it, and to get it on everybody's radar, and be excited about trying to move this forward as a more standard therapy. This is still a clinical trial, so it's not, it's not part of any standard therapies yet. We are using this quite regularly and have been very encouraged by the ease of which patients go through the transplant. It's still an allogeneic transplant; there still are many challenges there. However, these patients seem to be doing quite well, we're very encouraged, and so we keep going.

How does this approach impact patient outcomes as it relates to quality of life (QoL)?

The hard end points of 1-year relapse-free survival is obviously the most important to patients. However, going through an allogeneic transplant is obviously an incredibly difficult thing. Fortunately, I've only seen it [from] the doctor side, not [as a] patient.

However, I've seen many, many patients, and the quality of their life as they go through this experience is very important to all of us. As we saw these patients go through these studies, we felt like we were capturing something that was really important, and that is the ease [at which] many patients went through this experience, which just seemed different. It's hard to capture that.

It's really important for patients to speak and, and the way patients speak is in different ways. One way is through the QoL measures that they answer. This is [what they find] important, this is what they experiencednot what we say is happening. That's really important to hear that voice too. Those are data we're trying to collect. It's not so easy, because going through a bone marrow transplant is a poor QoL for everybody. But, by just to trying to capture this, [Orca-T seems] better than what we what we thought.

How has this changed the mindset of cell-based approaches in the community?

What has changed is the belief in the concept of cell-based therapies. A lot of these things are somewhat fanciful. It is also important to show that we can translate from an animal model [to a human]. There is a lot of criticism of animal modeling, because people say, "Well, it's nice for animal models, but it doesn't really translate into the clinic." Actually, my view is that because we don't actually follow the animal models, there are many compromises one needs to make. When you translate studies from animals to humans, there are many differences, and it's really important to try to follow them as carefully as you can within the limitations of what is possible. We were very engaged in that and tried to follow as carefully as we could. To me, that is very encouragingthat you can study things in animals that generate new concepts and be able to translate that into a clinical trial.

Obviously, with all of the caveats of an early-phase clinical trial, more time needs to pass, more patients to be treated, and you need to export [the treatment] to other centers. That's a really important point, because there are many things that get lost because, "it's too complicated. It's too expensive. People can't do it." I don't think anybody can do high-speed cell sorting, as a clinical project in a standard or standard cell-processing laboratory. It's above the level of what most processing laboratories can do.

References

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Negrin Shines Light on the Orca-T Story in GVHD - OncLive

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