According to Persistence Market Researchs new report, globalmale hypogonadism marketis slated to exhibit a steady expansion throughout the forecast period (2017-2026). Revenues from the global market for male hypogonadism are estimated to exceed US$ 3,300 Mn by 2026-end.

Governments Taking Initiatives to Spread Awareness about Male Hypogonadism Therapeutics

Lack of sex hormones, usually referred to as male hypogonadism has resulted into many health risks that include osteoporosis, heart disease, and cardiovascular diseases on the back of thinning of bones. Global male hypogonadism market comprises several patented brands that currently have high market penetration. Proliferation in geriatric population in tandem with rising incidences related to rheumatoid arthritis and obesity have been primary factors affecting prevalence of male hypogonadism globally. Mounting incidences of testosterone deficiency in male population is a key factor that prevalence of male hypogonadism has surged worldwide. Several governments around the world have been taking initiatives to spread the awareness on hypogonadism treatment procedures, for example testosterone replacement therapy (TST), in order to relieve the painful burden on patients and their families.

As low testosterone levels are increasingly associated with exacerbation of chronic conditions, it further results into disorders apropos to hypothalamic-pituitary-gonadal axis. Advent of TST has however enabled reduction in cases of male hypogonadism considerably. With growing awareness related to its treatment among patients, the market is likely to gain an uptick during the forecast period. Rising availability of the selective androgen receptor modulators (SARMs) has further sustained the market expansion. The development and high availability of SARMs has led toward the provision of improved treatment procedure to patients having androgen deficiencies, thereby influencing the market growth.

North America will continue to Dominate Global Male Hypogonadism Market

North America will continue to dominate the global male hypogonadism market, with more than one-third revenue share during the forecast period. In addition, revenues from the male hypogonadism market in North America will exhibit the fastest expansion through 2026, as compared to those from all the other regional segments comprised in the report. Europe and Asia-Pacific excluding Japan (APEJ) are also expected to remain lucrative for the male hypogonadism market. The market in APEJ will ride on a slightly higher CAGR than that in Europe through 2026.

Topical gels are expected to remain the most lucrative among drugs available for treatment of male hypogonadism globally, with sales projected to register the fastest expansion through 2026. Injectables will also remain a major revenue contributor to the market. Sales of injectable and transdermal patches are poised to reflect an equal CAGR through 2026.

Testosterone Replacement Therapy to Remain Preferred among Patients

Based on therapy, testosterone replacement therapy is expected to remain preferred among patients with male hypogonadism worldwide. Roughly 66% revenue share of the market is expected to be held by revenues from testosterone replacement therapy by 2026-end. Revenues from gonadotropin replacement therapy will remain slightly more than half revenues gained from testosterone replacement therapy throughout the forecast period.

Klinefelters syndrome is expected to remain the most prevalent disease type observed in the male hypogonadism market, and revenues from treatment of this disease will exceed US$ 1,800 Mn by 2026-end. Kallmann Syndrome and Pituitary Adenomas among disease types will also account for major revenue shares of the market by 2026-end.

Nature of global male hypogonadism market has been observed to be highly competitive. This can be mainly attributed to occupancy of many small as well as large suppliers. New companies entering the male hypogonadism market are leveraging opportunities related to treatment developments and innovations. Strategic alliances are likely to remain strong among vendors for producing and marketing drugs worldwide, thereby increasing their market reach. Active market players listed by PMRs report include Astrazeneca Plc., Merck & Co. Inc., Laboratories Genevrier, Bayer AG, Endo International Plc., Allergan Plc., Ferring, Finox Biotech, AbbVie Inc., Eli Lilly and Company Ltd., Teva Pharmaceutical Industries Ltd., and IBSA Institut Biochimque.

Read the original post:
Male Hypogonadism Market Expand at the Fastest CAGR of 3.7% Throughout the Forecast Quantity 2017-2026 - Zebvo

Recommendation and review posted by Bethany Smith

Biotech stocks extended their gains last week amid earnings news flow and the broader market strength. Large-cap pharma stocks saw particular strength.

Here are the key catalytic event a biotech investor should keep a tab on in the unfolding week.

Conferences

PDUFA Dates

The FDA is set to rule on Lipocine Inc (NASDAQ: LPCN)'s NDA for Tlando, or LPCN 1021 to treat hypogonadism in adult males. The PDUFA date is set for Saturday, Nov. 9.

Clinical Trial Readouts SITC Presentations

Alkermes Plc (NASDAQ: ALKS) Phase 1/2 data for ALKS 4230 in solid tumors and ALKS 4230 in combination with Merck & Co., Inc. (NYSE: MRK)'s Keytruda in solid tumors.

Celldex Therapeutics, Inc. (NASDAQ: CLDX) Phase 1 data for CDX-1140 in solid tumors (Friday, Nov. 8).

Pieris Pharmaceuticals Inc (NASDAQ: PIRS) Phase 1/2 data for PRS-343 in HER2-positive solid tumors.

CELYAD SA/ADR (NASDAQ: CYAD) Phase 1 data for CYAD-01 and FOLFOX in colorectal cancer (Friday, Nov. 8) and Phase 1 data for CYAD-101 in colorectal cancer (Saturday, Nov. 9).

Heat Biologics Inc (NASDAQ: HTBX) Phase 2 data for HS-110 and Bristol-Myers Squibb Co (NYSE: BMY)'s Opdivo in non-small cell lung cancer (Friday).

Oncolytics Biotech, Inc. (NASDAQ: ONCY) - interim Phase 1b data for Pelareorep and Roche Holdings AG Basel ADR Common Stock (OTC: RHHBY)'s Tecentriq in breast cancer (Friday).

View more earnings on IBB

Nektar Therapeutics (NASDAQ: NKTR) updated Phase 1/2 data for NKTR-214 + Opdivo in multiple cancers (urothelial carcinoma, melanoma, renal cell carcinoma, and non-small cell lung cancer) (Saturday).

Mirati Therapeutics Inc (NASDAQ: MRTX) initial Phase 2 data for sitravatinib in urothelial carcinoma (Saturday).

ASN Kidney Week Presentations

Allena Pharmaceuticals Inc (NASDAQ: ALNA) Phase 2 data for reloxaliase, or ALLN-177, in primary hyperoxaluria and Phase 3 data for reloxaliase in enteric hyperoxaluria (Friday).

See Also: BTIG: Crispr Could Be A Takeover Target For Vertex

Earnings

The earnings list is not comprehensive

Monday

Tuesday

Wednesday

Thursday

Friday

IPOs

Galera Therapeutics has filed to offer 5 million shares in an IPO, with an estimated price range of $14-$16. The company has applied for listing its shares on the Nasdaq under the ticker symbol "GRTX."

89bio, a biotech company focusing on therapies for NASH and other metabolic disorders, is planning a 4.375-million IPO at an estimated price range of $15-17. The company has applied for listing its shares on the Nasdaq under the ticker symbol "ETNB."

Gene testing company Centogene is proposing to offer 4 million shares in an IPO, which are to be priced between $14 and $16. The company has applied to list the shares on the Nasdaq under the ticker symbol "CNTG."

CNS Pharmaceuticals, which develops therapies for brain cancer and other CNS tumors, has filed for a 2.125-million share IPO. The shares, which are likely to be priced in the range of $4-$5, are to be listed on the Nasdaq under the ticker symbol "CNSP."

Tela Bio, which sells soft tissue implants used in hernia repair and reconstructive surgery, is set to offer 4 million shares in an IPO, with each share to be priced between $14 and $16. The company seeks to list the shares on the Nasdaq under the ticker symbol "TELA."

IPO Quiet Period Expiry

BioNTech SE ADR (NASDAQ: BNTX)Vir Biotechnology Inc (NASDAQ: VIR)

See more from Benzinga

2019 Benzinga.com. Benzinga does not provide investment advice. All rights reserved.

More here:
The Week Ahead In Biotech: Smid-Cap Earnings Deluge, SITC Conference In The Spotlight - Yahoo Finance

Recommendation and review posted by Bethany Smith

Hematopoietic stem cells (HSCs) are responsible for the constant replenishment of all blood cells throughout life. One of the major challenges in regenerative medicine is to produce tailor-made HSCs to replace the defective ones in patients suffering from blood related diseases. This would circumvent the shortage of donor HSCs available for the clinic. To achieve the controlled production of bona fide HSCs in vitro, in a dish, a better understanding is required of where, when and how HSCs are physiologically produced in vivo, in the living body. Researchers from the groups of Catherine Robin (Hubrecht Institute) and Thierry Jaffredo (UPMC, LBD IBPS, Paris) have found a previously unappreciated hematopoietic wave taking place in the bone marrow of late fetuses and young adults and producing HSCs from resident hemogenic endothelial cells of somite origin. This transient hematopoietic wave fills the gap between the completion of embryonic blood production and the beginning of adult bone marrow hematopoietic production in both chicken and mice. The results of this research are published on the fourth of November in Nature Cell Biology.

Endothelial origin of hematopoietic stem cells

The constant production of short-lived blood cells, needed for proper oxygenation of tissues and protection against pathogens throughout life, relies on a small cohort of HSCs. The first HSCs derive from specialized endothelial cells, named hemogenic endothelial (HE) cells, via an endothelial to hematopoietic transition (EHT). EHT transiently occurs in the main arteries, such as the aorta, during the embryonic development of vertebrates. The pool of HSCs is then amplified before migrating to the bone marrow where HSCs will reside during adult life. Whether EHT occurs past the embryonic stage and in other organs, such as the bone marrow, was unknown until now.

Hemogenic endothelial cells in the bone marrow

To find out whether EHT occurs past the embryonic stage and in the bone marrow, the researchers used a combination of experimental embryology, genetic, transcriptomic and functional approaches on chicken and mouse models. By tracing bone marrow-forming endothelial cells through fluorescent genetic labelling and live imaging analyses, they found that the entire vascular network of the bone marrow derives from the somites. The somites are segments of the body that will progressively form important tissues of the organism as the embryo develops, including bones, muscles and skin. Unexpectedly, the researchers found that some somite-derived endothelial cells produce HSCs and multipotent progenitors in the late fetus and young adult bone marrow, through the same EHT process that was thus far only seen in the embryo. These cells are molecularly very similar to the cells undergoing EHT or recently emerged HSCs in the embryonic aorta, with a prominent Notch pathway, endothelial-specific genes and transcription factors involved in EHT. The results therefore demonstrate that HSCs are newly generated past embryonic stages, from hemogenic endothelial cells from somitic origin and via EHT, the same mechanism that occurs in the embryo.

A new wave of blood cell production

The yolk sac of the embryo produces two partially overlapping waves of hematopoiesis. The first (primitive) wave gives rise to hematopoietic cells that last only during embryonic development. The second (definitive) wave produces various progenitors that migrate to the fetal liver to produce the immediate needed blood cells. These progenitors are sufficient for the embryo to survive until birth, when the aorta-derived HSC-dependent wave will take over. The transient hematopoietic production discovered in the present study fills the gap between the end of the yolk sac hematopoiesis and the bone marrow HSC-dependent production of blood cells. Indeed, the pool of HSCs that expanded in the fetal liver starts to colonize the bone marrow only just before birth. HSCs are present in very low numbers and time is most likely required before they find their final adult-type niches and start to differentiate/proliferate into more committed progenitors and mature blood cells. The transient hematopoietic wave that the researchers describe in late fetal and young adult stages might also prepare the bone marrow niches for the HSCs coming from the fetal liver.

Stem cell therapies

Defects in HSCs lead to various blood-related disorders and cancers that are partly treated by HSC transplantations. The controlled production of bona fide HSCs from pluripotent precursors remains very difficult to achieve in vitro, in a petri dish, and therefore requires a better understanding of the HSC production as it occurs physiologically in vivo, in the living body. Identifying all steps of hematopoietic production and the molecular events controlling this process is of fundamental interest and should help to devise innovative stem cell therapies for hematopoietic disorders in the future.

Go here to see the original:
Transient wave of hematopoietic stem cell production in late fetuses and young adults - Science Codex

Recommendation and review posted by Bethany Smith

Biohackers believe that we should be using all the technology available to make our bodies and minds work the best they can in everyday life. And they held a summit about it in Helsinki over the weekend

Most people who've heard of Biohacking think of electronic chips inserted under the skin - Cyborg stuff. But here they're promoting a wearable ring to measure the body.

People like Ramsey who's testing out a machine which steadily takes the body to air conditions you'd expect at high altitude...believe in using all the information and modern technology available to optimse human performance.

"I feel amazing - mentally and cognitively - like a stoic. I wake up every morning feeling like the Hulk," says Ramsey Morgan - Biohacker from Seattle, USA.

The movement is trying to make itself more mainstream and accessible.

"That can be like nutrition and diet, that can be taking a sauna, that can be just meditating, that can be injecting yourself with stem cells or something like that. All of these things are exapmles of Biohacking. You're changing your physiological state in order to achieve a certain goal," explains Siim Land - Estonian Biohacker.

And while most of us probably don't get enough sleep, the Biohackers say there's vibration technology to help.

"It affects to the nervous system by calming down the sypathetic side, the fight and fleet [flight] side. So basically, when you calm that down, the sleep comes naturally. You don't have to take any pills or anything," says Katja Nyman - Neurosonic.

One of the products here at the Biohackers summit is the Vielight Neuron, and our reporter, Jack Parrock tested it out.

"This a photobiomodulation device , so this applicator goes inside your nostril like that. And then the headpiece goes on top of your head," Gennady Lemud, VieLight Communications and Marketing Director tells our reporter.

The light rays being pumped onto my head and up my nose are intended to increase oxygenation in the blood and boost performance and happiness. But at well over 15 hundred euros, these devices aren't cheap.

Some Biohackers use blood tests to regularly check their liver function. One of the most controversial aspects of Biohacking is DNA testing. The medical community is still cautious and there are concerns about the data that's harvested by companies. They say there's nothing to worry about.

"We're looking at a few snips, a few genes...100...nothing. So we can't use that information for anything more than delivering information back to you as the consumer or the customer," says Chris Moore - Nordic Laboratories

It's not all so technical - getting in a sauna and a 4 degree celsius bath is enough for some Biohackers. But with the ever evolving technological world we live in - these guys think they're the future.

See the rest here:
Meet the biohackers seeking to turbocharge their bodies and minds - Euronews

Recommendation and review posted by Bethany Smith

Is there anything worse than dark circles under your eyes? No matter your age, skin type or skin tone, dark circles will always make your face look ten years older than you actually are. We all know the struggle of trying to get rid of dark circles, too. Its almost always an uphill battle, not just to remove the circles, but also to keep them gone.

There are many causes for dark circles under eyes. While the most common factor is a lack of sleep, they can also be caused by allergies, smoking, a poor diet, aging or even just genetics.

For some people, lifestyle changes like getting more sleep or eating healthier foods might improve dark circles. But the rest of us are going to need a little more help.

If you find the right one for your skins specific needs, an eye cream can work wonders in smoothing out your face even better than botox. The important thing to remember with any eye cream is to use it consistently without over-using it so that you are sure to prevent dark circles from forming without irritating the sensitive skin around your eye.

What It Does

- Uses clinically-proven ingredients like plant stem cells and squalane to nourish and revitalize skin

- Gives a more youthful, radiant and energized appearance to the eyes and face

- Wakes up the eyes with caffeine

Key Benefits

- Targets puffiness, dark circles and crows feet under the eyes

- Rejuvenates and hydrates skin for a more youthful appearance

- Supports hydration and skin elasticity

Promising Review

The most promising review for the Monat Eye Smooth is that the eye cream sold out within a month of launching and currently has a 13,000-person waiting list. While you can shop another eye cream in the meantime, we suggest you get on this wait list before it gets any bigger. Plus, if youre on the waiting list, Monat will throw in a free facial massager with your Eye Smooth.

What It Does

- Increases the skins natural collagen production to improve the appearance of under-eye skin

- High-performance formula that promotes healthy skin for bright eyes

- Restores the skins protective barrier to repair environmental damage

Key Benefits

- Deeply moisturizes skin and improves elasticity

- Reduces hyperpigmentation and dark circles

- Protects and revitalizes stem cells

Promising Review

New Staple - The perfect harmony of Revive & Recover Me - targeted for your eyes. Well done - I love it! - Marlena

Fre Brighten Me Anti-Dark Circles Eye Cream ($45)

What It Does

- Targets signs of aging with a brightening formula rich in Vitamin C

- Reduces the appearance of dark circles with banana power

- Improves concealer application and wear

Key Benefits

- Combats dark circles and bags under eyes

- Hydrates skin and locks in moisture

- Smooths out fine lines and wrinkles

Promising Review

I was never a big OH fan bc I tried a few products from this brand and they had my skin looking crazy on these streets and I dont play that. Bought this based on all the great reviews Ive seen, didnt expect anything really. Im 41, have a lot of fine lines under my eyes and under eye bags. Fast forward my fine lines have minimized (Im shocked) and my under eye area looks renewed. Idk if that makes sense but I look refreshed when I use this. The formula is creamy and melts into your skin. I look forward to using this product and Im looking at OH like yall did that. If you are on the fence about purchasing, Id say try it. For me it has exceeded my expectations. - barefootcontessa

OLEHENRIKSEN Banana Bright Eye Crme ($38)

What It Does

- Visibly reduces puffiness and dark circles under eyes in just one month of use

- Smooths out fine lines, wrinkles and crows feet within 12 weeks

- Uses retinol and a mineral complex for powerful results

Key Benefits

- Provides dramatic results while remaining gentle enough for daily use around the eyes

- Clinically proven to rejuvenate delicate, sensitive under-eye skin

- Improves the look of skin for an overall younger-seeming appearance

Promising Review

I've been using this product consistently for 20 yrs. For the past 5 yrs I've started using the rest of the roc line. I simply put it on before I put my makeup on and at night before going to bed. I'm now 44 and people think I'm in my late 20's...hey I'll take it! I've let everyone know what I use faithfully and they've tried it as well and love it! Never had an issue with skin irritations either. I highly recommend the whole line, but this product is off the chain. Thank you roc for a product that is as close to the fountain of youth as you can get! - Anonymous Target shopper

RoC Retinol Correxion Eye Cream ($15.99)

What It Does

- Uses an unprecedented and concentrated formula of clinical actives to get results

- Treats dark circles, puffiness and fine lines around eyes and eyelids

- Moisturizes the skin for a smoother appearance

Key Benefits

- Uses saccharomyces complex to reduce the appearance of dark circles

- Diminishes under-eye puffiness with alfalfa seed complex

- Creates a smooth look to the skin by pulling moisture in

Promising Review

Absolutely AMAZING! I inherited the puffy bags under my eyes from my dad and I didn't think any eye cream could beat genetics. I'm so glad I was wrong. I've been using for only two days (morning and night) and the bags under my eyes are half the size they were before. I will definitely purchase again! - Pallotta

Skinfix Barrier+ Lipid-Boost 360 Eye ($40)

What It Does

- Clinically proven to hydrate the delicate eye area without causing redness or irritation

- Softens the keep and helps it to retain moisture using a formula of 98.9% natural ingredients

- Perks up the appearance of the eyes

Key Benefits

- Provides a luminous, youthful-seeming complexion

-Combats under-eye puffiness

- Smooths sensitive skin gently

Promising Review

Absolutely love this cream. My face was so dry this winter, no amount of my regular moisturizer was working. I was miserable. With the Night Cream and the Cleanser for Sensitive Skin I'm so very happy. I use the Night Cream morning and night. The extra on my fingers gets rubbed into my hands and has made a them feel better too. And I have to say I'm not using very much. - psyche 1954

Burt's Bees Eye Cream for Sensitive Skin ($9.97)

What It Does

- Wakes your eyes for a rejuvenated, energized and brightened look

- Reduces puffiness and dark circles under the eyes

- Smooths out fine lines and wrinkles with peptides

Key Benefits

- Supports collagen production for a smooth texture and youthful appearance

- Removes dark circles and puffiness in the sensitive under-eye area

- Lightweight cream that also works as a makeup primer

Promising Review

Ive been on the hunt for the perfect eye cream and have tried many in different price ranges and this ended up being one of my favorites. Its not a miracle worker but It keeps my skin hydrated and I do notice my circles look a little lighter and less puffy. Its a great buy and certainly worth the money. Most of all I did not have any allergic reactions which is why I gave it 5 stars. Sadly I dont think any cream will make me look like I sleep 8 hours a night. - AnitaMarlene

The INKEY List Caffeine Eye Cream ($9.99)

Read the original:
7 Dermatologist-Approved Eye Creams That Work Better Than Botox - SheFinds

Recommendation and review posted by Bethany Smith

Diabetes is one of the leading health problems in our modern world and requires the careful management of a patients insulin levels. New research from Tufts University may make that process a little easier. In mouse tests, the team implanted beta cells that produce more insulin on demand, when theyre activated by blue light.

At the heart of both types of diabetes is insulin, the hormone that regulates blood sugar levels, allowing cells in the body to properly use it as energy. In type I diabetes, beta cells in the pancreas dont produce enough insulin, sometimes because the immune system destroys those vital beta cells. In type II diabetes, a patients cells stop responding to insulin, or the pancreas cant keep up with demand, meaning blood glucose levels spike to dangerous highs.

Managing the condition requires constant monitoring of blood sugar levels and boosting insulin levels as needed, either by directly injecting the hormone or through drugs that amplify the beta cells production of it.

For the new study, the Tufts researchers engineered pancreatic beta cells that can produce insulin on demand in this case, that demand is pulses of blue light. The beta cells were engineered with a gene that creates an enzyme called photoactivatable adenylate cyclase (PAC) essentially, when these enzymes are activated by blue light, they produce a molecule called cyclic adenosine monophosphate (cAMP).

In turn, this molecule instructs the beta cell to produce more insulin, but interestingly, it will only do so when theres already a high level of glucose. That helps to prevent a common complication of diabetes treatments, where producing too much insulin can cause the body to consume the available glucose too quickly, resulting in low blood sugar.

To test the new technique, the Tufts team implanted their engineered pancreatic beta cells under the skin of diabetic mice. The researchers found that the cells produced between two and three times more insulin when triggered by blue light and high glucose levels. Importantly, when they fired up the blue light while glucose was low, there was no bump in insulin, indicating that the failsafe worked.

In this way, we can help in a diabetic context to better control and maintain appropriate levels of glucose without pharmacological intervention, says Emmanuel Tzanakakis, corresponding author of the study. The cells do the work of insulin production naturally and the regulatory circuits within them work the same; we just boost the amount of cAMP transiently in beta cells to get them to make more insulin only when its needed.

Similar studies have shown promise in managing diabetes with implanted beta cells either synthetic versions or natural ones produced from a patients own stem cells. Theres still plenty of work to do before this type of treatment makes it to human trials, but the researchers say that using light is a step in the right direction.

There are several advantages to using light to control treatment, says Fan Zhang, first author of the study. Obviously, the response is immediate; and despite the increased secretion of insulin, the amount of oxygen consumed by the cells does not change significantly as our study shows. Oxygen starvation is a common problem in studies involving transplanted pancreatic cells.

Ultimately, tiny sources of light could be embedded alongside the cells, allowing doctors to trigger them remotely when needed. Or they could be automatically activated by a glucose sensor, to fully close the loop.

The research was published in the journal ACS Synthetic Biology.

Source: Tufts University

See the original post here:
Light-activated pancreatic cells produce insulin on demand - New Atlas

Recommendation and review posted by Bethany Smith

Transparency Market Research, in its latest market intelligence study, finds that the global Stem Cell Umbilical Cord Blood market registered a value of ~US$ xx Mn/Bn in 2018 and is spectated to grow at CAGR of xx% during the foreseeable period 2019-2029. In terms of product type, segment holds the largest share, while segment 1 and segment 2 hold significant share in terms of end use.

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More:
Global Cryopreservation Equipments in Stem Cells Market to Witness Significant Revenue Growth During the Forecast Period, 20192023 - Health News...

Recommendation and review posted by Bethany Smith

George Van Tassels post-war life started off typically enough. In the years after WWII, he was working as a tool and dye maker at Douglas Aircraft in Santa Monica, and living with his wife Eva and three daughters in a 900-square-foot bungalow in Sawtelle. By the end of the decade, he had relocated the family to tents next to a giant rock in the Mojave Desert where he communicated with space people who shared secrets about telepathy, immortality, and instructions to build a hemispherical umbrella dome that became known as the Integratron.

Architectural historian Daniel Paul landmarked the unusual structure in 2018, and will explain the art and science of Van Tassels midcentury wonder at Zebulon on Wednesday, November 6. In advance of the event, we talked to Paul about aliens, Howard Hughes, and more.

What is the Integratron?

Its a circular, wooden, two-story, hemispherical umbrella dome structure built by George Van Tassel near Landers starting in 1958. Its primary purpose was as a life extension machine, but Van Tassel thought it might be able to undertake time travel and antigravity experiences. It was intended to be the primary building of a ten-acre campus called the College of Universal Wisdom to educate people about the teachings and guidance of the space people.

Who are the space people?

Van Tassel had an interest in the metaphysical sciences before he moved to the desert and evolved into speaking to space beings. He started receiving transmissions from what he called the space people and he claims to have been visited by one called Solganda one night in 1953. Dozens of other space people were channeled through his mind. He called these forms of communication an Omnibeam.

Photo by Daniel Paul

What did the alien say?

He told him that the problem with human beings is that by the time you learn what you need to know youre old and then you die and that life must be extended. He ran an interplanetary spacecraft convention there from the 1950s through the 70s. They were the first large gatherings in the U.S. of UFOlogists.

How was the Integratron built?

Architecturally it is quite phenomenal. The upper level is a dome of all exposed wood. Solganda told him not to use any metal in the construction. The design is based on an aircraft fuselage. Its a hemispherical umbrella dome made of Glulam ribs connected with wooden dowels. There is a 1.5 ton concrete and Micarta non-metallic oculus made by Westinghouse for aerospace use.

Photo courtesy of Daniel Paul

Where do you think the design came from?

Van Tassel appears to have worked with Howard Hughes on an all-wood aircraft called the D-2; it was the precursor to the Spruce Goose. If you look at pictures of the interior of the Spruce Goose and the Integratron dome theyre very similar.

Photo by Daniel Paul

What was this thing supposed to do? How did it work?

There were supposed to be 64 aluminum dirods, or extended beams, intended to spin and generate electrostatic energy. He was reading about Nikola Tesla and others, and Van Tassel thought he could generate 50,000 volts and regulate the energy of a human cell. Cells give off energy and the Integratron was going to generate trillions of negative ions. As cells age they no longer give off the proper charge, which in turn causes aging and health problems. He wanted to recharge the cells because he thought that spirits were basically electricity.

Photo courtesy Daniel Paul

Did he extend his own life?

Although it was a life extension machine, Van Tassel himself ran out of time. He passed away in 1978 and all the machinery intended to be inside was never installed.

What happened after he died?

His wife kept publishing his newsletter Proceedingsfor a while, but other people tried to take ownership, including somebody who wanted to paint it lavender and call it the Lavender Disco. In the 90s, a couple bought it and wanted to fire it up but that never happened. Three sisters from New York now own it. They are running a very popular sound bath experience. I had a sound bath but I can never be fully clean in there because I cant hear out of my right ear.

Photo by Daniel Paul

Why are you doing this talk at a music club?

It seems like they have rather diverse programming. They do interesting film events and did something with the Unarius Academy UFO group. With a name like Zebulon, youd think they might be pretty open to different things.

Whats the future of the Integratron?

I got it listed on the National Register of Historic Places in 2018. The property owner was interested in protecting it for the future and was very sensitive to the legacy of Van Tassel and his creations. The psychiatrist Carl Jung called California Classic saucer country. We have an openness to the metaphysical and to high tech. Theres a lot of Echo Park vibes up there now. Its a beautiful space, the sound baths are highly regarded, and people love it.

Integratron: The Extended Life of a Life Extension Machine, A Slide Lecture, Wed., Nov. 5, 8 p.m.;Zebulon, 2478 Fletcher Dr., Elysian Valley.

RELATED: Ten Interesting Ways to Explore Joshua Tree Like a Local

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The Integratron Has a History as Interesting as It Looks - LA Magazine

Recommendation and review posted by Bethany Smith

Treat longevity as a national issue. Once again, the UK (lets not forget that their healthcare costs are less than half of those in the US!) offer a great example here. Theresa May, the British Prime Minister, announced a plan called HLE+5 (HLE is an abbreviation for healthy life expectancy), aiming to extend healthy lifespans of their citizens by 5 years by 2035. It would be great to see a similar initiative in the US.

Asa part of my interview series with leaders in healthcare, I had the pleasure to interview Sergey Young. Sergey Young is Founder ofLongevity Vision Fund, one of the worlds top three investment funds specializing in life extension. Sergey is also on the Innovation Board of the XPRIZE Foundation (which is most known for its Ansari XPRIZE and Google Lunar XPRIZE competitions). Sergey Young is also the Development Sponsor of Longevity XPRIZE, a global initiative to cure aging, and a member of the Financial Advisory Board of the Parliamentary Group on Longevity in the UK, helping to devise the national strategy on longevity. Based between the UK & US, Sergey Youngs mission is to extend healthy lifespans of one billion people around the world on both sides of the Atlantic through impactful socially responsible investments and by setting a personal example after all, his own goal is to live to 200.

Thank you so much for doing this with us! Can you tell us a story about what brought you to this specific career path?

Sure! My personal story can appear quite mundane at first, but it is one that affects95 millionAmericans. It all started with a routine visit to a doctor, where my blood tests which I neglected for 7 years, thinking I was in perfect health showed that my cholesterol was very high, which put me at risk of heart disease.

The only treatment offered by my doctor at the time was to take statins (cholesterol-reducing drugs), which I would have to take for the rest of my life. I definitely did not want to live on a pill forever, so I kept pushing my doctor for alternatives. Eventually, the doctor suggested I try a Mediterranean-style diet (lots of healthy fats, no sugar, etc.), which worked in bringing my cholesterol down to a normal range without any medication. Since then, I developed an interest in health and longevity, and decided to use my investment experience (I had been managing a $2 billion private equity fund for 20 years by that point) to accelerate longevity breakthroughs and to make them more affordable and accessible in general. This is howLongevity Vision Fundwas launched and the company mission was shaped.

Can you share the most interesting story that happened to you since you began leading your company?

I went to a regenerative medicine conference in Vatican City last year, just at the outset of launchingLongevity Vision Fund. Apart from meeting the Pope and seeing Katy Perry in person there, what astonished me the most was when Peter Diamandis my mentor, friend and the Founder of XPRIZE, was telling the audience about how technology will change over the next couple of decades, allowing us to extend our lives to at least 150. Then he paused, his face lit up with excitement, and asked who in this audience wants to live to 150. Obviously, I immediately raised my hand, but saw Peters expression change to shock and surprise only a very small percentage of people in the room had raised their hands. I was one of the few.

Id assumed most people would jump at the chance to live longer, if it was offered. But clearly thats not the case. In fact, in a recent Pew Research report on radical life extension,56% of American adults said they would not want to live to 120. The opportunity to extend our lives is within reach, and people might

turn it down. So Ive set out to dispel misinformation, fear and disbelief that this topic commonly incites. Not only through my work atLongevity Vision Fund, but also by sharing information in a book called Growing Young, which I hope to release in Q3 2020. I want people to get educated on longevity rather than get scared of it times have changed and the breakthroughs in medical science and technology now make it entirely realistic to live to 100 and beyond all within our lifetime!

What makes your company stand out? Can you share a story?

Probably that the company is driven by someone who plans on living to 200! On a more serious note, Longevity Vision Fund has a focus specifically on affordable and accessible technology. Our goal is to democratize longevity, so we look for scalability and breakthrough potential in the companies we invest in.

A great example of how we make longevity more accessible and affordable is our investment in EXO Imaging, which develops portable ultrasound imaging devices at a very low price point. In fact, it makes ultrasound imaging so affordable that it actually becomes accessible to every healthcare provider in the world. Imagine being able to get your ultrasound scan done at your family physician, without having to be referred to a hospital (with the associated waiting time and costs this can bring!). Or using the portable device anywhere it might be required at emergencies by ambulance paramedics, or even the patient themselves (after a short training). And since EXO Imaging uses AI to process the scan, it has the potential to maintain, and even exceed, the accuracy of ultrasound scans that rely on interpretations of doctors without the support of this technology. This means that ultrasound scans can become as common and mundane as checking your blood pressure at your doctors office. Imagine the relief, affordability and improved access that cancer, thyroid and many other patients can enjoy!

Can you share with our readers about the innovations that you are bringing to and/or see in the healthcare industry? How do you envision that this might disrupt the status quo? Which pain point is this trying to address?

I use3 Horizons of Innovationto map the longevity & healthcare innovation space:

At Longevity Vision Fund we focus mostly on horizons 1 and 2. The main pain point we are trying to address is making sure that longevity is accessible and affordable to everyone in the world. We do this by supporting scalable technologies with breakthrough potential that can democratize longevity. For example, our portfolio company Insilico, an AI in drug discovery company, has demonstrated its ability to identify design, synthesize and validate a novel drug candidatein just 46 days, compared to the typical 23 years required for a standard approach used by the majority of pharma.

What are your 5 Things I Wish Someone Told Me Before I Started and why. (Please share a story or example for each.)

Lets jump to the main focus of our interview. According tothis studycited by Newsweek, the US healthcare system is ranked as the worst among high income nations. This seems shocking. Can you share with us 35 reasons why you think the US is ranked so poorly?

You are a healthcare insider. Can you share 5 changes that need to be made to improve the overall US healthcare system? Please share a story or example for each.

Thank you! Its great to suggest changes, but what specific steps would need to be taken to implement your ideas? What can individuals, corporations, communities and leaders do to help?

Everybody can implement these steps in their lives as of today! If you are interested in learning more, you can read Blue Zones by Dan Buettner or go to my websitesergeyyoung.comwhere I put out information on longevity (absolutely for free) as part of my mission to extend lifespans of one billion people. And if you are reading this that includes you!

What are your favorite books, podcasts, or resources that inspire you to be a better healthcare leader? Can you explain why you like them?

Here are my three favorite books:

Another great resource is Abundance 360 by my friend and XPRIZE Founder Peter Diamandis. It offers some great guidance on understanding how to navigate exponential technology and use it to achieve Moonshots.

How can our readers follow you on social media?

Follow me onLinkedin(Sergey Young), Facebook and Twitter (@sergeyyoung200)

Thank you so much for these insights! This was so inspiring!

Original post:
The Future of Healthcare With Sergey Young, Founder of Longevity Vision Fund - Thrive Global

Recommendation and review posted by Bethany Smith

BNP Paribas Leasing Solutions and 3stepIT announce that their joint venture "BNP Paribas 3 Step IT" started trading in October.

This new entity offers a complete and more sustainable way to manage technology lifecycles. It delivers a service based on circular economy principles; a service that anticipates the needs of companies looking for more flexible and sustainable "product as a service"2 financing solutions.

BNP Paribas 3 Step IT combines the strengths, expertise and geographical cover of the European leasing leader, BNP Paribas Leasing Solutions, and the Finnish specialist in IT life cycle management (management, refurbishment in own logistics centres and re-marketing), 3stepIT, to take the latters successful approach out of its Nordic stronghold and deliver it across Europe.

BNP Paribas 3 Step IT provides a complete service to companies to help them manage technology investments (mainly smartphones, tablets, PCs and laptops). The service adds value at all points in the lifecycle. It helps: Analyse their needs to develop a lifecycle planProvide the funding to select and acquire the planned equipmentMonitor and manage equipment in use: where it is, who pays, how much it costs, when to replace it, as well as automating many routine IT administration tasksReturn equipment at the end of the contract, for secure data destruction followed by refurbishing for resale, when the value recovered helps reduce rental costs

In practice, this approach helps clients improve their IT service level, with up to date equipment; and provide IT devices at a lower overall cost. It also helps run IT in a more sustainable way, because the devices are refurbished, rather than dumped.

We refurbish 97% of returned devices for re-use, with less than 3% being recycled. Our focus on sustainability also confers sustainability on our clients own use of IT. Extending the life of equipment displaces the manufacture of new product and spreads the manufacturing carbon footprint across two users. Including manufacture, transport and power costs in the calculation, this reduces the carbon footprint by 36%. Electronic waste is the fastest growing waste stream on the planet, and the source of 70% of landfill toxic waste. Re-use reduces clients e-waste contribution by around 48%.

Sustainability is a growing factor in IT planning. While 15% of organisations say it is a consideration today, a further 67% say they intend to integrate sustainability into their IT plans within the next two years3. A circular economy lifecycle approach, that delivers product life extension for over 97% of returned devices, will interest these organisations.

"Since we announced this joint venture, many international companies have wanted to learn more. The lifecycle management service meets their business needs, and aligns with their values in terms of responsibility. Becoming more sustainable is increasingly a competitive differentiator, and a consideration for clients, partners and investors. As well as serving clients broader needs, this alliance is in perfect sync with the BNP Paribas Group strategy to support circular economy initiatives," said Charlotte Dennery, CEO of BNP Paribas Leasing Solutions.

"We are delighted to take our solution across Europe. BNP Paribas 3 Step IT will offer a more sustainable approach to using technology, on a large international scale - a breakthrough for a circular economy business model, and a response to our customers demands for a global service, said Carmen Ene, CEO of 3stepIT.

1. European countries covered by the alliance:Joint venture: Austria, Belgium, France, Germany, Italy, the Netherlands, Poland, Portugal, Spain, Switzerland and the United Kingdom.Commercial partnership: Denmark, Estonia, Finland, Latvia, Lithuania, Norway, Sweden.

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BNP Paribas and 3stepIT commence tech leasing joint venture - Finextra

Recommendation and review posted by Bethany Smith

There is a reason the Liberty City community was once known as Hog Eye Country, and as of late the name has been revived as the area once again is being inundated with wild hogs.

Bo Camp (whose great grandparents, Della and Ben Chapman, settled in the area in the mid-1800s) said, There are actually several stories pertaining to the name. One had to do with a man whose neighbor let his hogs get into his pasture. He supposedly caught the pigs and sewed their eyes shut to prevent them from coming back in. But, I doubt that seriously happened even though my great grandparents actually had a post office in their home at one time called the Hog Eye Post Office.

My grandparents then bought 200 acres at the hub of the area where the four-way stop sign is now, and my mother was born in a house on one of those corners. They used to kill hogs and hang them in the smokehouse. The hogs that were not needed for butchering would be turned loose along the Sabine River banks to feed off the acorns and other stuff and then rounded back up again in the fall to kill for enough meat to get through the winter months.

Of the 4 to 5 million feral hogs in the United States, an estimated 2.6 million call Texas home. Feral hogs can be found in 99% of Texas counties and cause an estimated $52 million in damages to Texas agricultural enterprises each year, according to the Texas A&M Agricultural Life Extension.

Pat Sheets, who lives near the Sabine River, said, Something has got to be done. The wild hogs have destroyed my pretty green pasture, the dam across my pond and are now in my front yard. The holes are terrible almost two feet deep but long where they have rooted. If anyone needed something buried, I could easily do so.

Pat, age 81, is gaining the reputation of being the next Wyatt Earp having shot a hog recently near her deer feeder. She said, They are mean and they are dangerous. I had a wild boar chase my dog almost right up to me, and I shot at the ground to keep from accidentally hitting my dog. The hog turned after I shot, otherwise it would have gotten me. I was okay while it was happening, but the minute I sat down on my porch I started shaking.

One of her neighbors caught a photo of a 400 lb. hog on his camera last week and another neighbor, David Bardwell, has shot three of the hogs in his pasture within the last two weeks, according to Pat.

She readily admits, I am getting too old to stay up late at night when they come up. I need to be able to do things during the daytime. I did have a young boy shoot one off my back porch and that was around midnight.

I have dragged the holes with my front-end loader of the tractor attempting to fix it. When you drive over them it is like driving over a rub board.

Deer season will start soon and Pat plans on calling in professional hunters two weeks into the season to have enough time for her own deer hunting.

Eddy Holley, who has pastureland near Hwy. 31 East, said, You should see my pastures. They have rooted all the way across my land and have now crossed over the highway. Wild hogs are smart. They will come out late in the evening and go to the same place for two to three nights in a row then they will move. A lot of people think you can trap them, but that is not easy. Billy Higginbotham, who retired from the Texas A & M Research & Extension Center stressed through his seminars that you have to put bait in the traps first to get the feral used to going into the pen. Then set the trap.

I dont have much luck with the traps, I have better luck with Stay Tuf fence. I have learned it is easier to fence them out than to try to get rid of them after they have destroyed it. By the way, in Texas, it is legal to shoot a hog because of the amount of damage they do.

According to Eddy, owner of Kilgore Feed Company, I personally believe the corn deer hunters put out is a drawing card for the animals. They were not used to food being readily available, having to root for grub and other stuff before. If you stop and think about it, one sow can have a litter of 10 or more pigs each time. That is at least 30 pigs per year from one sow, so you can easily see why we are having such a problem.

Damage to vehicles from the hogs is enormous, according to Gerad Waits, manager of Patterson Body Shop in Kilgore: So far, we have seen 13 vehicles that have hit hogs, he said. Drivers dont know what they hit a lot of times, but we can tell by the hair left on the vehicle. We have also repaired vehicles damaged by 41 deer, one cow, 18 raccoons and, the last couple of weeks, four coyotes. And we havent made it to the end of the year yet.

Nonetheless, the hogs have become a serious problem. As for me, I think I will stick with Pat Deadshot Sheets.

MOTHER NATURE helped make the Soup & Pie Luncheon at St. Lukes United Methodist Church a big success again this year. That cold front arrived just in time according to that bunch.

DONT forget to turn your clocks back one hour this Saturday evening or at 2 a.m. Sunday morning officially if you care to stay up that late. We will gain that extra hour of sleep, but for the most of us driving home in the dark.

MAY HIS LOVE AND LAUGHTER fill your hearts and your homes throughout the week. In the meantime, we may be reached at chitchatlinda@aol.com or 903-984-2593.

Continued here:
ChitChat | It's a little wild in Texas | Lifestyles - Kilgore News Herald

Recommendation and review posted by Bethany Smith

The provinces economic forecast is looking promising for 2020, but outside the oil industry all is not rosy.

Thats according to APECs Economic Forecast for the Atlantic region, released yesterday.

Newfoundland and Labradors real GDP is expected to rebound by 2.7 per cent in 2019, led by stronger oil production and mining. For 2020, APEC is forecasting 2.4 per cent real GDP growth, as oil production is expected to increase by 9 per cent.

Capital investment meanwhile is expected to improve by 16 per cent in 2019. the first growth since 2015, with a further 4 per cent advance in 2020.

Despite growth in the oil industry, the rest of the economy of Newfoundland and Labrador continues to struggle. Employment is up 1.4 per cent over the first nine months of the year, but has fallen by 8,000 since peaking.

Outmigration continues to be an issue, weakening the local labour force. The population fell by over 8,000 people since it peaked in late 2016.

Retail sales are down nearly 2 per cent in the first seven months of the year, while the housing market is also suffering from outmigration according to APEC. The sale price of existing homes is down by 4 per cent in the first nine months of 2019.

9 per cent growth in oil production will be somewhat muted as Terra Nova production is scheduled to be offline for six to seven months in 2020 as its drilling vessel undergoes an asset life extension. APEC is also expecting employment to drop slightly in 2020 as work on Muskrat Falls winds down.

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Economic Forecast Up Thanks to Oil, But All Other Areas Struggling - VOCM

Recommendation and review posted by Bethany Smith

VANCOUVER Nov 6, 2019 (Thomson StreetEvents) -- Edited Transcript of Lucara Diamond Corp earnings conference call or presentation Tuesday, November 5, 2019 at 2:00:00pm GMT

Lucara Diamond Corp. - Founder, President, CEO & Director

* John P. Armstrong

Lucara Diamond Corp. - VP of Technical Services

* Zara E. Boldt

Lucara Diamond Corp. - CFO & Corporate Secretary

Joh. Berenberg, Gossler & Co. KG, Research Division - Analyst

Good morning. My name is Pam, and I will be your conference operator today. At this time, I'd like to welcome everyone to the Lucara Diamond Q3 2019 Results Conference Call. (Operators Instructions) Ms. Eira Thomas, please begin your conference.

Eira Margaret Thomas, Lucara Diamond Corp. - Founder, President, CEO & Director [2]

Yes. Yes, they do hear you. Please go ahead.

Eira Margaret Thomas, Lucara Diamond Corp. - Founder, President, CEO & Director [4]

Sorry, I had music in the background there. Okay. Let's start this again. Good day, everyone, and thank you for joining us for a combined call to discuss the results of our recently released underground feasibility study together with our Q3 results.

Joining me today, we have Zara Boldt, our CFO; Dr. John Armstrong, our Vice President of Technical Services; Ayesha Hira, our Vice President of Corporate Development and Strategy; and Gord Doerksen, Principal at JDS Energy and Mining and our feasibility study lead on the underground project.

Before we start, I would just like to remind everyone that all of the speakers on the call today will be making forward-looking statements. Please refer to the cautionary statements on Slide 2 of the webcast for more detail.

So addressing the big news first. Lucara is delighted to be reporting strong positive economic results from its recently completed bankable feasibility study, contemplating a 15-year expansion of its 100%-owned Karowe diamond mine in Botswana. Karowe, which has been in production since 2012, is a unique top-of-class diamond asset renowned for its consistent recovery of large, high-value, type IIA white diamonds and the only mine in history to ever recover 2 +1000 carat diamond. Over the past 7 years of open-pit mining, Karowe has mined and sold 2.6 million carats, generated $1.5 billion in revenues and has consistently delivered high operating margins, better than 60%.

Since 2014, Lucara has also paid out more than $270 million in dividends, well in excess of the total capital invested to build and upgrade our mine. With the completion of our 2019 bankable underground feasibility study, we could also confidently state that this is just the beginning. Resource work completed since November 2017 identified a much larger economic opportunity at depth than was previously envisaged driven by the increasing contribution of higher-grade, higher-value EM/PK(S) ore. Underground expansion would double the mine life outlined in the original 2010 feasibility study, deliver net after-tax cash flow of $1.22 billion and gross revenues of $5.25 billion. The underground alone will deliver close to $4 billion of those revenues.

It is also important to note that approximately $200 million in revenues generated from exceptional high-value diamonds like the Lesedi La Rona and the Constellation were not included in our economic analysis and represent a significant opportunity for revenue upside. We are highly confident of further large high-value stone recoveries, especially as we mine deeper and gain access to higher-grade, higher-value EM/PK(S) ore. We just can't predict exactly when they will come. Based on the recoveries to date, these exceptional diamonds could add upwards of $500 million in additional revenues over the proposed new life of mine.

Another key takeaway from this study is that the cost to expand our mine underground is affordable and can be largely funded out of cash flow and anticipate the short payback period of under 3 years. What's more? Operating margins remain healthy despite the application of conservative diamond pricing models that take into consideration the current difficult market environment. Lucara's short-term view is that the market is now stabilizing. Longer term, the fundamentals are expected to strengthen in line with supply shortfalls from mature depleting mines in Australia and Canada.

Our return to diamond prices observed in 2015 would nearly double the NPV of this project to $1.4 billion at a 5% discount.

Engagement with the Botswana government has been ongoing, and with the feasibility study complete, we are now in a position to file for a mining license extension to cover the remaining open pit and proposed underground mining operation. To this end, we will be meeting with the government in the near term to present the results of the study and finalize our plans for stakeholder engagement.

To take us through the results of the underground feasibility study in more detail including assumptions and key inputs, I would now like to turn the presentation over to Dr. John Armstrong.

--------------------------------------------------------------------------------

John P. Armstrong, Lucara Diamond Corp. - VP of Technical Services [5]

--------------------------------------------------------------------------------

Thank you, Eira. Good morning and good afternoon to everyone. I'm very pleased to provide this breakdown of the results of the study. So my plan is to run through the key findings of the study. And I think on the one slide you were looking at, we can see some of the key findings. Basically as part of the feasibility study, the resource model has been updated with conversion from inferred to indicated between 400 and 250 meters above sea level within the South lobe and an extension of the inferred classification from 250 meters above sea level to 66 meters above sea level, which is, again, against the previous model which had the base of the inferred at 250 meters above sea level and the kimberlite remains open below the 66 level.

I would say that overall, the mining method selection was data driven and the method chosen is long hole shrinkage, and we'll get into the details of that as the presentation proceeds, provides access to high-value, high-grade ore [earning] in the underground mine life. With the underground mine ramping up coincident with the depletion of the open-pit reserves and the proposed schedule does not require processing of stockpiles to mitigate against any production shortfalls during the transition from open pit to underground.

The payback period happens what we're mining in competent granted host material. And overall, we're going to maintain ore to the plants of 2.6 million to 2.7 million tonnes a year. And the combined open pit and underground scenario, as you see on the slide, provides a strong economic argument for proceeding.

I'd like to mention the technical team. Lucara engaged with JDS Mining and Energy (sic) [JDS Energy and Mining] to be the study lead under the direction of Gord as Eira indicated. JDS assembled a group of their own internal consultants and external consultants that is world class, extremely experienced, are subject matter experts with proven track record of project delivery and mine construction.

Right? In terms of the data elements, Eira did touch on this, but Lucara and Lucara Botswana have been engaged with the government of Botswana from the early stages of the study, and we've maintained that communication. As Eira indicated, we'll be sitting down with the government in the next few weeks to present the results of this feasibility study to initiate our stakeholder engagement and proceed with filing for a mining life extension to cover the remaining open pit and proposed underground mining operation. The projects in its conclusions have been very much data driven using historical data, operational data obtained from 7 years of mining, processing, diamond recovery and diamond sales from Karowe. And as indicated earlier, we have an extensive set of new information obtained over the course of the feasibility study.

Identified key focus areas of hydrogeology, geotechnical constraints of the kimberlite and host rocks have been addressed through this intensive set of work programs. The data collection started back in 2016, ran through the PEA process which was completed in 2017 and has been substantially updated and augmented by the feasibility study, and you can see and read some of the metrics on this particular slide. I won't run through all the details. And ultimately, the quality and abundance of data was deemed sufficient and suitable for the level of the study being presented.

I'll touch quickly on these next set of slides, which is the -- on the resource update. I mean the [space] underpins the whole decision to proceed with the feasibility study. We've updated the geological model. We've updated the resource model. This has resulted in the -- a new base of indicated resource sitting at 250 meters above sea level. Previously, that sat at 400 meters above sea level. So we've added 150 meters of indicated within the South lobe, and we pushed the inferred down to 66 meters above sea level.

The work has been supported by detailed core logging of geotechnical and delineation holes that were drilled as part of the 2018-'19 FS study, complemented by additional dry density, detailed petrography and microdiamond data, which is augmented by our previous work in 2018.

Now we can look at the Mineral Reserves Statements (sic) Mineral Reserve Statements for the remaining open pits and now classification of probable mineral reserves within the underground portion of the deposit, and this table is represented here also in the press release. And you can see the split between the open pit and underground reserves and the split between the dominant rock types. Within the underground, we have 33.5 million tonnes with just over 5 million carats available for the feasibility study as a probable mineral resource.

Now I'll touch on diamond pricing. A set of size frequency distribution and value models were generated for the EM/PK(S) and the M/PK(S) domains within the South lobe. These are the dominant rock types present within the South lobe. And based on data gained over the last 2 years or so, we've been able to develop these independent SFD and value models for both the E and the M/PK(S). The parcels used to model the SFDs are very robust. The M/PK(S) model is informed by approximately 410,000 carats or greater than a year's production. The EM/PK(s) model is informed by approximately 45,000 carats of targeted production and compared against a set of some 150,000 carats of daily EM/PK(S) production where I have SFD sizing data for that particular daily production.

The average price per carat models are a function of the size frequency distribution and value by size class. The value models for the EM/PK(S) and M/PK(S) have been adjusted in the plus 10.8 size category to reflect current weakness in the price achieved for large, high-quality rough to our tender sales. The average price proposed for the feasibility study are based on a view that, that portion of the market will see price improvement by 2025 but at levels that are still conservative against the market high and also against pricing used in 2018.

I'd just like to remind everyone looking at this particular histogram plot on the bottom that our achieved average prices that have -- over the last -- since 2014 represent a blend and are weighted by the proportions of carats recovered and sold from the various lobes, and you get an idea of what that looks like in terms of the pricing metrics on that histogram slide.

This next slide is a couple of schematics cross sections of the AK6 kimberlites. One of the most significant findings of the various resource upgrade drilling programs that have been running since 2016 has been the determination that the EM/PK(S) units became increasingly significant with respect to diamond content and volume at depth within the South lobe, especially below 400 meters above sea level. And now based on operational data produced -- based on operational data, we are confident that some of the world's largest gem-quality diamonds have been sourced from the EM/PK(S). What's also shown here on this diagram is the split between the indicated and inferred at the 250 meter above sea level. You can see in the shaded diagram on the left where we have the EM/PK(S) in purple becoming the dominant rock type as we get deeper in the resource. And you can see within the inferred, there's another unit now coming in called KIM-3, which has attributes more similar to the M than the EM/PK(s), sitting within the inferred category.

Next slide, please. Now we're going to talk about the underground mine design and the selection of long hole shrinkage as the preferred technique. Trade-off studies were completed that examined a variety of underground options including block caving, assisted block caving, sub-level cave, sub-level retreat. The AK6 kimberlite and the host rocks of the crew sequence present a very unique setting. Particularly at Karowe from surface, we have about 140 meters of the salt which overlie about 120 meters of sandstones locally with interbeds of red mudstone that are very poor quality and are water-bearing and followed by a mudstone domain and 140-meter package of carbonaceous shales with discontinuous coal seams.

So this package is about 400 meters of sedimentary sequence overlie basement granites. The kimberlite of the South lobe and the basement granites are a very good rock quality with UCSs of 130 to 150 MPa with sparse jointing. The remainder of the host rock package are of reasonable rock qualities. However, there is a substantial thickness of weaker material with UCSs of 30 to 40 MPa within the 140-meter sequence of carbonaceous shales, intercalated coal seams that lie on top of the basement granites.

Regional in situ horizontal stresses are low in the country rock, roughly half that of the vertical stress, while the pipe has elevated horizontal stresses as evidenced by the results of wireline overcoring in situ stress tests that were conducted as part of the geotechnical data program. The South kimberlite is much stronger than normal, and the in-depth test work, data analysis, including detailed core logging, geotechnical core logging, the in situ stress measurements, eliminate natural caving as an option and present a good opportunity for stoping. The mining method selected is referred to as long hole shrinkage, and the plan is to systematically drill and blast the kimberlite on a vertical retreat basis. Drilling and blasting will occur from a series of sub-level space of 100-meter vertical intervals, access via 2 vertical shafts and internal ramp system developed within the granite and also developed within the kimberlite itself to avoid lateral development within the weak carbonaceous shale sequence.

Long hole shrinkage, with this technique, a significant portion of the blasted muck is left in the stope during blasting and stoping or during the actual mining activity. That acts to assist and stabilizing the host rock, and we only extract the swell during this drill and blast phase.

We'll see a few schematics coming up of mucking will take place from a number of draw points on the 310 level or 310 meters above sea level, which will form the main extraction level. Once the column of South lobe is fully blasted, stope is drawn empty by mucking out of the draw points. Production rates are sufficient to maintain the 2.6 million to 2.7 million tonnes per annum of ore to the ore processing facility.

The underground portion of the mine alone will produce an average 392,000 carats a year, mining from the 700- to 310-meter above sea level elevations, with a 13-year production life after an initial 5.5 years of preproduction development and ramp up the full underground production. The resource economically favors long hole shrinkage over sub-level caving for its bottom-up approach. It take advantage of the higher-value kimberlite at depth, coupled with low operating costs and derisk the project with respect to geotechnical and hydrogeological issues of host rocks.

This next slide is an isometric diagram of the underground -- [Karowe's] underground workings. So we're going to walk through this in a series of steps. You can see the 2 vertical shafts. There's the production shaft and the ventilation shaft. And on the next slide, we're going to see some more details around the -- kind of the physicality of those particular items. I just want to reinforce the advantages of this method when we're looking at this isometric diagram. We get extraction of the highest-value rock first. We have low and delayed dilution. We have development and production of the underground, can occur while simultaneously with pit operations. So we'll be developing the mine at depth where we're still operating in the pit. We reduced the dewatering risk by how -- using grouted shafts and delay surface breakthrough into the open pit for 5 production years. We have minimal developments in poor ground and the development of the extraction level, which we'll discuss on the 310 level, is designed to manage natural caving should it occur. And we have the ability to rapidly increase the draw on the mucking rate once the resource is fully blasted.

We have flexibility, we have less risk, and we have the ability to mine below the 310 level within the indicated resource down to 250 and potentially beyond. The shafts that we sunk at the same time with the ventilation shaft dedicated as a heavy lift, providing access initially on the 680 level for the purpose of a drill level and establishment of a dewatering gallery. Water control and hydrogeological context of the deposit and host rocks are key elements of the mine plan. The 680-level dewatering gallery will provide the necessary infrastructure and access to dewater the overlying red mudstones in advance of open-pit mining in the preparation for underground mining and bridging of the crown pillar into the open-pit scheduled for 2029.

The main extraction level, 310 level, has a layer of more typical of caving mines with a total of 56 draw points, underground pressures and basically a normal layout for rock-handling systems underground. The place oriented 2 21-tonne skips for conveyance to surface. Total lateral developments of the proposed underground is approximately 16.3 kilometers on 8 levels with 2,800 meters of vertical development in shafts and then raises. Development of the extraction level and shaft design allow for deeper ore to be accessed below 310.

This series of summary tables with the main aspects of the design for the shafts, the levels, the extraction. We get 8 levels, 6 of which are accessed from the shaft, 2 of which are accessed by -- through internal ramping either up from the 320 level or down from the 680 level. The key takeaway here, I think, is to drive our attention to the extraction level design with 56 draw points from 5 panels that brings significant operational and extraction flexibility. The potential to increase production in the period post-2029 once the stope is fully blasted is there. The ore tonnes per meter of development at 2,000 tonnes a meter aligns with more lines of caving operations and sub-level-type operations. The powder factor and hole burden is aligned with the current open-pit operations. So basically, the drill and blast regime that we'll be using underground is almost identical to the same that we're using in the open pit at the present time. And we have blast studies that indicate that our comminution and our size distribution of the muck will be easily handled within those draw points.

This is a cross-sectional view, a bit of a cartoon for stope design and sequence. The pyramidal sequence is proposed for the drilling and blasting of the stopes at Karowe. The blasting sequence will create a dome-shaped back at the top of the blasted volume to maintain the stability of the back. Stopes will be blasted sequentially upward in 17.5-meter increments until a 30-meter sill pillar is left between the drill panel and the stope back. And that final 30-meter sill will then be blasted and terminate access to the drill panel of that location. Drilling will take place from sub-level spaced approximately 100 meters apart, using in-the-hole hammer rigs, and the idea is to drill downholes. The key points to take away from this diagram -- and basically, we will start at the extraction level; blast the drawbells; proceed up to the next level, the 380 level; and initiate blasting from the 480 level down and progress that stoping upward. Once we get into the domain of the pipe which has the carbonaceous shales and the sedimentary rocks as the country rock will leave a skin of kimberlite behind, which will provide additional support against dilution, and then we'll take this skin later in the mine life as we prepare to reach the crown pillar into the bottom of the open pit.

Drilling and blasting activity is proposed at a rate of around 21,000 tonnes per day with mucking of the swell of approximately 7,500 tonnes a day to draw down the stope to accommodate the blasting of the next 17.5-meter lifts. The bulk of the host rock is of good quality. And this, combined with the cylindrical shape of the ore body, prevents low risk for substantial waste entry, and the kimberlite skin will provide additional confining support against the host rock as does the broken muck before a final drawdown.

This particular slide now shows that we're going to get into some of the financial and resource aspects of the proposed underground operation. This is an illustration of available carats by rock type and level. I think what we can see is we're going to see this carry through to the next set of slides. As you can see that at the bottom level, so the 250 and the 300 level that the amount -- the volume of carats available is dominated by the EM/PK(S). And as you can see from the diamond pricing and the coarse nature of that size distribution, that is also the highest-value rock available within the column. And we'll see that, as I say, flow through the next set of slides.

The next set of slides also do address indicative and estimated volumes in tonnes and carats, costing and expense estimates. And I would refer you back to the cautionary statement at the beginning of the presentation while we go through these slides.

We're looking now at the indicative production schedule. And what this shows is basically the distribution of tonnes by rock type for the open pit and the -- basically, the crossover to underground tonnes in 2025. The key takeaway from this particular diagram is that when we look at the value of the material that's coming out of the underground, we see that the peak in [2030], 3 or 4 years of underground production, dominated by the EM/PK(S). And you can see that from that particular diagram. And then mid-underground mine life as the M/PK(S), not unexpectedly, becomes a more significant driver of the volume since this particular unit becomes more significant in the shallower portions of the South lobe that we see a decrease in the overall value. And we'll see -- later, we see a bit of a drop-off in the carats, but we're still maintaining in excess of 300,000 carats a year. And there's no expectation to see treatment of stockpiles during that transition from open pit to underground. We see the stockpiles come through in the last 3 years of the mine life where we process remaining working stockpiles and the life of mine stockpile.

This next slide shows some production metrics, which is basically showing carat production by year and by source. And we can see a boost in the carat and the influence of the EM/PK(S) and the ramp-up in the early period of the underground with production of approaching 500,000 carats a year and over 400,000 carats a year for a number of years in the early part of the underground mine life for a total recovered carats from the underground of 7.8 million, an average grade of 14 cpht and dragging in those stockpiles at the end of the mine life for processing.

Next slide, please. We'd like to now touch on preproduction CapEx, sits at USD 514 million. This is driven, obviously, by the mine development with shaft sinking costs running around $160 million of that and the remaining underground development sitting in around the same, $160-odd million. We will need additional power at Karowe to support the underground operation in terms of hoisting and ventilation. So we -- as part of the feasibility study -- and shown in the numbers for the feasibility study is a new 29-kilometer long, 132-kV power transmission line running from a new substation constructed by Botswana Power Corporation into the mine site, and that will provide sufficient power for the current requirements and the underground development. Work on this power line process is ongoing in parallel with the feasibility study. But again, I say all the costs for that power line are shown in the feasibility study economics.

Other infrastructure required to support the underground operation include various surface buildings and facilities adjacent to the 2 vertical shafts, a construction camp and expansion of coarse and fine tailings facilities. Based on understanding gain from the mining, milling and diamond recoveries from unweathered hard (inaudible) kimberlite over the last 4 years in conjunction with additional test work as part of the feasibility study. The current flow sheet is deemed suitable for processing of the underground sourced kimberlite and diamond recovery in line with the resource model.

Now we're going to run through some of the economics. I won't spend a lot of time on these slides. In the interest of time, everyone can read the numbers. The first one is the stand-alone underground scenario with the life of mine average price per carat of $725, 13 years of mining and milling of underground-only ore with a 20.8% internal rate of return at 16% post-tax IRR and less than a 3-year payback.

We're showing now on this particular slide the combined underground and open pit, laid out similar to the previous one. We have 7.84 million carats that could be recovered at an average price of $670 a carat. This is the combined open pit and stockpile scenario which were the end of the mine life with $1.2 billion post-tax cash flow; 56 million tonnes treated; $5.25 billion in gross revenue and an after-tax NPV of 5% of $718 million; and again, less than a 3-year payback; and average life of mine operating costs of just $28.43 a tonne ore processed.

This slide can be married with the previous pie diagram, showing the breakdown of the preproduction estimated capital. And we can also show here estimations on sustaining costs for both the underground and open-pit operations for the $514 million of preproduction cap and an estimation of $208 million of life of mine for sustaining and closure costs.

I think we'll emphasize here that the underground operation will continue. What's been established by the open pit is a high-margin producer with respect to operating cost per carat. And you can see the breakdown on the left-hand side of that -- or the right-hand side of the slide of the cost per carat from the various aspects of the operation, and again, with an over in excess of $500 a carat margin.

This is -- the next slide depicts the operating costs for the underground, the unit cost per tonne milled, unit costs, dollar per carat and life of mine estimates. Then now we're showing the underground-only operating estimates. Again, for underground mining processing, G&A and the total number is reflected on this particular diagram.

This slide shows the open-pit underground post-tax cash flow. As I indicated, the estimated schedule maintains the mill throughput of 2.6 million to 2.7 million tonnes a year without a production dip. The main takeaway from this is the big capital spend that you can see in the early part mainly coming through in 2021 during the shaft-sinking period and then strong post-tax cash flows in the early years of the underground. This is the influence of the higher-grade, higher-value plus 400,000 carat production per annum that will come in the early years, dominated by the EM/PK(S). In terms of sensitivities, this is also presented in the press release. Obviously, the main sensitivity is diamond price.

And then I think we should talk a little bit about some of the project risks. Obviously, project execution, which involves procurement, labor financing, are key risks that we will have identified and we'll work very hard to mitigate against. The schedule in terms of dewatering and assuring no different production, the dewatering schedule is tight and requires us to get down to that 680-meter level to allow us the longest period of time possible for dewatering of the sandstones and the mudstones that we'll be mining through with the underground stoping and the open pit.

Opportunities. There are short-term opportunities with respect to the newly updated resource model in terms of pit optimization and scheduling, and this work is ongoing. Opportunities exist below the 310 level for additional ore access from the underground workings. There's a potential for increased production rates post-2029. The shafts at 2.7 million tonnes a year of conveyance are not at full capacity, so there's the ability for additional hoisting. And then we would look at increased mill throughput. We have resource potential in the North and Center lobes that will require drilling and work from underground. And obviously, the recovery of high-value stones will have positive impacts to project economics.

Looking at the indicative schedule is the timing. We can basically look at this, and I will speak to a little bit in the next steps. We can see from this particular schedule that 2020 is not extremely capital intensive. And that main expenses come through in the second half of the year as we prepare for shaft sinking, and then we can see that the early works with the camp construction and some of the other surface work and the power line coming in, in mid-2022 to align with finishing and completion of the shafts, fitting in the shafts and getting ready for the ramp-up of underground production through 2023-'24, ramping up to full capacity '25-'26.

With that, I would like to thank JDS and Gord for the excellent work that he and his team have done delivering this quality study in an extremely compressed time frame. So it's a, like I said, a very quality piece of work. It shows the way forward, I think, for Lucara and delivering a positive economic results and a very unique asset with some very unique geology and some very unique diamonds.

With that, I will pass the call back over to Eira.

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Eira Margaret Thomas, Lucara Diamond Corp. - Founder, President, CEO & Director [6]

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Thank you, John. To sum up, Lucara is highly encouraged by the results of the Karowe underground Feasibility study which has outlined a much larger economic opportunity than first envisaged and represents an exciting, world-class growth project for our company. A significant portion of the cost to expand our mine underground can be funded from cash flow, and the investment is expected to be paid back in under 3 years as we've mentioned numerous times.

The mining method is ideal for allowing us to exploit the highest value part of the ore body first. It is important to reiterate that the study has used conservative assumptions around diamond price, an important lever in the economic analysis. A return to diamond prices observed in 2015 would significantly reduce or even eliminate the requirement for external financing and would more than double the NPV at a 5% discount.

In the first half of 2020, as John has stated, the company will focus on detailed engineering and early procurement initiatives as financing options are explored. The anticipated capital requirements represent less than 10% of the initial CapEx estimate for the underground project overall, and the company anticipates funding these initial expenses from cash flow.

I, too, would like to thank Gordon and JDS. And I would like to now turn it over to Zara Boldt, our CFO, who is going to take us through a summary of our Q3 results.

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Zara E. Boldt, Lucara Diamond Corp. - CFO & Corporate Secretary [7]

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Thank you very much, Eira. Starting on Slide 31. We've got some highlights from our third quarter. Operating performance in the third quarter was strong, with mining and processing activities and our operating cost per tonne of ore processed at $31.06, all tracking well to guidance. Revenue in the current quarter was almost identical to total revenue in the same quarter last year despite the number -- higher number of carats sold. We sold 5 diamonds for more than $1 million each and 1 diamond for more than $2 million in the third quarter tender. The gem-quality blue and pink diamonds recovered in the third quarter will be sold in our December tender.

We completed 5 sales through Clara in the quarter, and the total value transacted on the platform doubled to USD 2.4 million. Our customer base has also grown significantly with 27 participants on the platform as of September 30, and it's now over 30 participants at the present time.

You will have noted our decision to suspend the payment of the quarterly dividend, effective immediately. With the results of a positive feasibility study for development of an underground mine at Karowe now in hand, our Board of Directors determined that the suspension of the dividend would be in the best interest of the company and its shareholders. We are of the view that the best use of our available cash is directed to early works, including detailed engineering, procurement initiatives and project financing. The anticipated capital requirements in 2020 represent less than 10% of the preproduction CapEx estimate, and we do expect that our cash flow next year will be sufficient to support that work while we arrange external financing to supplement the expected contribution of our cash flow from operations to develop the underground.

We anticipate that our external financing requirements could be met with some form of debt financing. At this time, we are not contemplating an equity issuance. We will provide further guidance as this progresses.

Moving to Slide 32. We look at our financial highlights for the 9 months ended September 30, 2019. Similar to our third quarter results, our revenue of USD 136.5 million on a year-to-date basis is almost identical to the same period last year. Consistent with the last few quarters, we continue to recover smaller, lower-value diamonds. While still profitable, the smaller goods do impact the average price per carat sold. And you can see that impact in the decrease from $564 to $436 per carat sold in the chart at the bottom left.

Our net income to date is $4 million or $0.01 per share. Consistent with previous quarters this year, our net income has been significantly impacted by depletion and amortization expense of $38.1 million. In the third quarter, we recorded a 24% increase in our quarterly operating expense as compared to Q3 2018. This increase results from a combination of several things, including an increase in the average cost per tonne mined, lower volumes of total tonnes mined, an increase in total tonnes processed and anticipated increases in certain consumables and labor expense. Despite this increase, our year-to-date cost per tonne processed at USD 31.06 is trending to the lower end of our guidance.

Our adjusted EBITDA is about 10% less than our 2018 comparative at USD 50.2 million, with the main driver of this difference, the increase in operating expenses. Cash flow per share from operations was $0.08 per share in the current 9-month period as compared to $0.09 per share in 2018.

Moving to Slide 33. We have our operational highlights presented on a year-to-date basis. The results are fairly consistent with our operational performance during the first half of this year, and we've spoken previously about the differences when compared to the same period last year.

Moving to Slide 34. We have our 2019 outlook. We have revised our 2019 guidance for revenue, narrowing our range to between $170 million and $180 million for the year. We have also narrowed our guidance for carats recovered and sold, estimating that we should be between 400,000 and 425,000 carats for those ranges due to consistently higher recoveries mainly in the smaller size classes. We've also narrowed our waste mining guidance to be between 6.5 million and 7.5 million tonnes this year. Finally, we expect our cost per tonne mined to be at the lower end of our revised guidance of USD 32 to USD 34 per tonne processed.

Moving to Slide 35. We've got our capital structure. As of September 30, we had cash of $4.8 million, nothing drawn on the working capital facility but $50 million available. Despite the current downturn in the diamond market, we are generating enough cash to operate our business, develop the Clara platform and to have been a steady dividend payer. The feasibility study has outlined strong economics, and we are confident that our external financing requirement will be modest with attractive financing options available to supplement the expected contribution of our cash flow from operations to fund the underground project.

With that, we have concluded the formal portion of the presentation, and we'll now open the floor for questions.

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Questions and Answers

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Operator [1]

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[Operators Instructions) Your first question comes from Edward Sterck, BMO.

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Edward Christopher Sterck, BMO Capital Markets Equity Research - Analyst [2]

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Just wanted to ask perhaps a bit of a detailed question on the blasting phase. So that -- presumably, that is all happening upfront before you start drawing ore. And I just wanted to ask whether the cost of the blasting is included in the capital cost. And then if not, just to -- I guess that -- the cash -- online cash costs are going to be higher during that blasting phase and before the serious drawdown of the rock pile commences.

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John P. Armstrong, Lucara Diamond Corp. - VP of Technical Services [3]

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Edited Transcript of LUC.TO earnings conference call or presentation 5-Nov-19 2:00pm GMT - Yahoo Finance

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Recommendation and review posted by Bethany Smith

If you hit enough specific diseases, youre getting at the core aging components that are common to all of them, Church, a Wyss core faculty member, said in an interview Monday. Gene therapy gives you a testable therapy at scale in mice. And we can move from mice to dogs and then to humans. Were focusing on the reversal of age-related diseases so well be more healthy and youthful later in life.

The research is part of a broader emerging field, sometimes called geroscience. Its advocates believe that the best way to treat a variety of illnesses from cancers and heart disease to Alzheimers and macular degeneration is to attack the aging process itself.

Were taking a holistic approach, said Noah Davidsohn, a former research scientist in Churchs lab who is first author of the study. Rather than attack specific diseases, were trying to make patients generally healthier and, in the process, getting rid of as many age-related diseases as possible. Nobody wants to be old and in a wheelchair and not doing anything.

Bostons biomedical hub has become a hotbed of geroscience research.

Last winter, 16 of the worlds top longevity scientists, including Harvard scientist David Sinclair, professor of genetics and director of the Paul F. Glenn Center for the Biology of Aging, formed a Boston-based academy that will seek to spotlight medical research on extending human life and developing drugs to slow the aging process. The nonprofit Academy for Health and Lifespan Research will share research and lobby governments in the United States, Europe, and elsewhere to increase funding and create new paths to approve age-slowing therapies.

Previous studies in the field have also sought to slow aging and extend healthy life spans through small molecules that increase blood flow and endurance, or weed out zombie cells that send out toxins causing age-related maladies. But the Wyss Institute is the first to use therapy that combines genes to boost protein levels that diminish with aging. The genes were selected from a database developed over the past decade at Churchs lab.

We looked at the ones that had the biggest impact individually and then wanted to see if they would work more effectively in pairs and triples, Church said. Such an approach, he said, had the greatest potential to target multiple diseases through a one-and-done injection into the blood or muscle, a simple procedure akin to getting an influenza vaccine shot.

When deployed against obesity, type II diabetes, heart failure, and renal failure, a single formulation ... was able to treat all four diseases, according to the study published in PNAS. These results emphasize the promise of gene therapy for treating diverse age-related ailments, and demonstrate a new approach of combination gene therapy that may improve healthspan and longevity by addressing multiple diseases at once.

San Diego-based biotech startup Rejuvenate Bio, founded by Church and a pair of coauthors of the PNAS study, Davidsohn and Daniel Oliver, is pursuing a gene therapy to fight age-related diseases. The company has already begun working with the Cummings School of Veterinary Medicine at Tufts University in North Grafton to test the gene therapy combination in dogs.

Davidsohn, chief technology officer at Rejuvenate, said the company is focused for now on developing and marketing a treatment that can extend the health span of dogs, which can suffer from a range of age-related illnesses including heart and kidney problems, obesity, dementia, and hearing and vision loss similar to those afflicting humans.

His own 5-year-old dog, Bear, whom Davidsohn adopted while working in the Wyss Institute lab, was an inspiration and now holds the honorary title of chief inspiration officer at Rejuvenate. The company was launched in stealth mode about a year ago and now has eight employees.

While dogs will be an important market in their own right for the combination gene therapy, Davidsohn said, We would be happy if this ended up in humans.

Church said testing the experimental therapy in dogs is likely to take about two years. Then, if regulators approve it, clinical trials could begin in humans. But even if all goes well, he said, the gene therapy probably wont be available as a marketed product for more than a decade.

By then, he said, the cost of a gene therapy which now can top $1 million per patient for rare diseases could drop to thousands of dollars per patient in what would be a much larger market to treat multiple age-related diseases.

Some supporters of age-slowing research, such as Jay Olshansky, public health professor at the University of Illinois at Chicago, have cautioned against expectations that scientists can radically lengthen life spans. Instead, they believe, the goal should be, as Olshansky puts it, pushing out the red zone, the time of frailty and disability at the end of life.

Church, however, has a more ambitious vision.

The important thing is getting good at age reversal, he said. If age reversal truly works, there is no upper limit on how long healthy lives can be extended.

Robert Weisman can be reached at robert.weisman @globe.com. Follow him on Twitter @GlobeRobW.

Correction: An earlier version of this story incorrectly characterized the status of the collaboration between Rejuvenate Bio and George Churchs Wyss Institute Lab.

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Harvard study advances gene therapy in fighting age-related diseases - The Boston Globe

Recommendation and review posted by Bethany Smith

Harvard synthetic biology pioneer George Church generated some buzz last year when he co-founded Rejuvenate Bio with the goal of reversing aging with gene therapy. Now, he and his co-founders say they have compelling early evidence in mice that they can use the technology to reverse multiple age-related diseases at once.

The researchers gave the mice three genes associated with longevity, either alone or in various combinations. The genes were FGF21, sTGF2betaR and alpha-Klotho. In previous experiments, they had shown that mice genetically engineered to overexpress the genes experienced benefits in both their health and life spans.

This time, they used mice that were not genetically engineered but rather models of obesity, Type 2 diabetes, heart failure and kidney failure. They wanted to prove their hypothesis that giving the mice extra copies of the genes might confer similar health benefits. They found that some combinations did improve or reverse symptoms, they reported in the journal Proceedings of the National Academy of Sciences.

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The Harvard team discovered that a combination of FGF21 and sTGF2betaRcould treat all four diseases. FGF21 administered on its own reversed weight gain and Type 2 diabetes, and, when it was combined with sTGF2betaR in mouse models of kidney failure, it lowered kidney atrophy by 75%.

Administering all three genes together turned out to be an unsuccessful strategy, however. Mice that received that combination had worse outcomes than the other animals did, the team reported. The researchers believe there may have been an adverse reaction between FGF21 and alpha-Klotho, but they said further experiments would need to be designed to confirm that.

RELATED: George Church founds cryptocurrency-fueled genomics firm

Rejuvenate Bio was launched from Churchs lab at Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering in 2017 but is still largely in stealth mode. It generated some attention last year, after it started reaching out to dog owners with the opportunity to enroll their pets in a trial of a gene therapy to treat mitral valve disease. The heart condition affects some breeds in outsized numbers, including Cavalier King Charles spaniels.

The potential benefits of the three genes Churchs team investigated for the newly published study are well known. FGF21, for one, has been shown to play a beneficial role in insulin resistance and fat metabolism. And last year, researchers partially funded by diabetes drug maker Novo Nordisk discovered that a variant in the gene is present in some people with naturally low levels of body fat.

Last year, Yale researchers discovered that beta-Klotho promotes weight loss, glucose metabolism and insulin sensitivity by binding to FGF21. And a separate team led by New York University published their discovery that alpha-Klotho facilitates FGF23 signaling, which in turn modulates the aging process.

Rejuvenate Bios Church said in a statement that a one-time gene therapy to address multiple age-related diseases could offer several benefits for patients and that the mouse trial was a major step toward the companys efforts to develop gene therapies for human use.

"This research marks a milestone in being able to effectively treat the many diseases associated with aging, and perhaps could lead to a means of addressing aging itself," Church said.

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Gene therapy to fend off aging? Buzzy Harvard startup Rejuvenate Bio says it works in mice - FierceBiotech

Recommendation and review posted by Bethany Smith

As people age, they tend to develop diseases such as heart failure, kidney failure, diabetes, and obesity, and the presence of any one disease increases the risk of developing others. Traditional drug treatments, however, each target one condition. That means patients often have to take multiple medications, increasing both the risk of negative side effects and the likelihood of forgetting one.

New research from the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School (HMS) suggests that it may be possible someday to tend to multiple ailments with one treatment.

In the Wyss study, a single administration of an adeno-associated virus (AAV)-based gene therapy, which delivered combinations of three longevity-associated genes to mice, dramatically improved or completely reversed multiple age-related diseases, suggesting that a systems-level approach to treating such diseases could improve overall health and lifespan. The research is reported in PNAS.

The results we saw were stunning and suggest that holistically addressing aging via gene therapy could be more effective than the piecemeal approach that currently exists, said first author Noah Davidsohn, a former research scientist at the Wyss Institute and HMS who is now chief technology officer of Rejuvenate Bio. Everyone wants to stay as healthy as possible for as long as possible, and this study is a first step toward reducing the suffering caused by debilitating diseases.

The study was conducted in the lab of Wyss core faculty member George Church as part of Davidsohns postdoctoral research into the genetics of aging. Davidsohn, Church, and their co-authors homed in on three genes that had been shown to confer increased health and lifespan benefits in mice that were genetically engineered to overexpress them: FGF21, sTGFR2, and Klotho. They hypothesized that providing extra copies of those genes to nonengineered mice via gene therapy would similarly combat age-related diseases and bring health benefits.

The team created separate gene therapy constructs for each gene using the AAV8 serotype as a delivery vehicle, and injected them into mouse models of obesity, Type 2 diabetes, heart failure, and renal failure both individually and in combination with the other genes to see whether there was a positive synergistic effect.

FGF21 caused complete reversal of weight gain and Type 2 diabetes in obese, diabetic mice following a single gene therapy administration, and its combination with sTGFR2 reduced kidney atrophy by 75 percent in mice with renal fibrosis. Heart function in mice with heart failure improved by 58 percent when they were given sTGFR2 alone or in combination with either of the other two genes, showing that a combined therapeutic treatment of FGF21 and sTGFR2 could successfully treat all four age-related conditions, therefore improving health and survival. Administering all three genes together resulted in slightly worse outcomes, likely from an adverse interaction between FGF21 and Klotho, which remains to be studied.

Importantly, the injected genes remained separate from the animals native genomes, did not modify their DNA, and could not be passed to future generations or between living animals.

Achieving these results in nontransgenic mice is a major step toward being able to develop this treatment into a therapy, and co-administering multiple disease-addressing genes could help alleviate the immune issues that could arise from the alternative of delivering multiple, separate gene therapies for each disease, said Church, who is also a professor of genetics at HMS and professor of health sciences and technology at Harvard and MIT. This research marks a milestone in being able to effectively treat the many diseases associated with aging, and perhaps could lead to a means of addressing aging itself.

Church, Davidsohn, and co-author Daniel Oliver are co-founders of Rejuvenate Bio, a biotechnology company that is pursuing gene-therapy treatments for dogs. Each holds equity in Rejuvenate Bio.

The finding that targeting one or two key genes has therapeutic effects in multiple diseases makes enormous sense from the perspective of pathophysiology, but this is not how drugs are normally developed. This ability to tackle several age-related diseases at once using gene therapy offers a potential path to make aging a more manageable and less debilitating process, said Wyss Founding Director Donald Ingber, who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Childrens Hospital, as well as professor of bioengineering at Harvards John A. Paulson School of Engineering and Applied Sciences.

Reference: Davidsohn et al. 2019.A single combination gene therapy treats multiple age-related diseases. PNAS.https://doi.org/10.1073/pnas.1910073116.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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SELBYVILLE, Del., Nov. 5, 2019 /PRNewswire/ -- The global Cancer Gene therapy market'srevenue is expected to surpass USD $2.5 billion by 2025, according to a new research report by Global Market Insights, Inc. Rising government initiatives in emerging economies for promoting developments in gene therapies will positively impact the cancer regenerative medicine market's growth. The government often implements several laws and initiatives to motivate scientists and researchers to perform extensive analysesof gene therapies. Furthermore, the government also funds various studies that are carried out for developing molecular therapies utilized in the treatment of cancer. The aforementioned factors should escalate the industry's growth.

There have been several advancements in the biotechnology sector that have proven beneficial for the industry's growth. Several viral vectors have been introduced in the market that work efficiently for carrying out gene transfers. Researchers vigorously work on studying the efficacy and efficiency of the viral, as well as non-viral, vectors that are utilized in gene therapy. Newly developed viral vectors are capable of inhibiting the growth of tumor-inducing genes and are preferred by biopharmaceutical companies. Moreover, healthcare professionals working on gene therapy have started trusting and preferring these viral vectors for treating cancer patients. Therefore, growing advancements will ensure the availability of superior quality vectors for gene transfer, which will foster the market's growth.

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The types in the cancer gene market are categorized into in-vivo and ex-vivo. The in-vivo segment of the cancer gene therapy market was valued over USD $350 million in 2018 and will experience substantial growth throughout the analysis period. In-vivo gene therapy is a cost-effective option since it avoids the tedious process of removing cells from a patient's body. Furthermore, in-vivo cancer gene therapy is widely expected to treatcystic fibrosis, which positively influences business growth. However, in recent times, several high-profile, adverse events pertaining to gene therapies were recorded that has reduced its demand, therebylowering the pace of segmental growth.

Based on product, the global market is bifurcated into viral vectors and non-viral vectors. The viral vectors segment of cancer gene therapy is anticipated to foresee around 23% growth throughout the analysis timeframe. Adenovirus is one of the highly preferred viral vectors that has commendable transductional efficiency that raises its adoption. Moreover, theadenovirus vector reduces the risk of mutagenesis. Besides, other viral vectors are also efficient and enable long-term DNA expression, reducing the mortality rate in patients suffering from cancer. The aforementioned factors will spur the viral vectors' segment growth.

Cancer Gene Therapy Market Growth, By Product

5.1. Key segment trends

5.2. Viral vectors5.2.1. Market size, by region, 2014 2025 (USD Million)5.2.2. Adenoviruses5.2.2.1. Market size, by region, 2014 2025 (USD Million)5.2.3. Lentiviruses5.2.3.1. Market size, by region, 2014 2025 (USD Million)5.2.4. Retrovirus5.2.4.1. Market size, by region, 2014 2025 (USD Million)5.2.5. Adeno associated virus5.2.5.1. Market size, by region, 2014 2025 (USD Million)5.2.6. Herpes simplex virus5.2.6.1. Market size, by region, 2014 2025 (USD Million)5.2.7. Vaccinia virus5.2.7.1. Market size, by region, 2014 2025 (USD Million)5.2.8. Others5.2.8.1. Market size, by region, 2014 2025 (USD Million)

5.3. Non-viral vectors5.3.1. Market size, by region, 2014 2025 (USD Million)

5.4. Others5.4.1. Market size, by region, 2014 2025 (USD Million)

Browse key industry insights spread across 95 pages, with 120 market data tables and eight figures and charts from the report,Cancer Gene Therapy Market Size By Type (Ex-vivo, In-vivo), By Product (Viral Vectors {Adenoviruses, Lentiviruses, Retrovirus, Adeno Associated Virus, Herpes Simplex Virus, Vaccinia Virus}, Non-viral Vectors), By End-use (Biopharma Companies, Research Institutes), Industry Analysis Report, Regional Outlook (U.S., Canada, Germany, U.K., France, Italy, Spain, Japan, China), Price Trends, Application Potential, Competitive Market Share & Forecast, 2019 2025," in detail, along with the table of contents:

https://www.gminsights.com/industry-analysis/cancer-gene-therapy-market

The end-use segment of cancer gene therapy includes biopharmaceutical companies, research institutes and others. The research institutes segment held around a 40% revenue share in 2018. Significant segmental growth can be attributed to the increasing demand for viral vectors by research institutes that work on cancer gene therapies. Research institutes constantly focus on assessing the efficacy of gene therapies by using different vectors. Moreover, vector manufacturing companies develop superior quality viral, as well as non-viral, vectors that will positively influence the segmental growth.

The U.K. market accounted for around USD $35 million in 2018 and is projected to witness momentous growth during the analysis timeframe. The increasing adoption of cancer gene therapy due to considerably high purchasing power has augmented the cancer gene therapy market growth in the country. Furthermore, the increasing prevalence of cancer has positively influenced the industry's growth. According to a study, in 2017, around 164,901 people died from cancer in the U.K., which creates demand for advanced gene therapies for treating cancer.

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Cancer Diagnostics Market Statistics 2025: Breast cancer is one of the most frequent cancers among womenacross the globe. According to the World Health Organization (WHO), about 2.1 million women are suffering from breast cancer each year. Also, breast cancer rates are higher among women in more developed countries than in developing and under-developed economies. A few prominent players operating in the global market are Abbott, Roche, Siemens Healthcare, Danaher Corporation, Becton, GE Healthcare, Dickinson and Company (BD), Janssen Diagnostics among others.

https://www.gminsights.com/industry-analysis/cancer-diagnostics-market

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cancer-gene-therapy-market.jpg Cancer Gene Therapy Market Forecasts 2025 Cancer Gene Therapy Market is set to register over a 22% CAGR up to 2025, driven by the rising prevalence of cancer in developed, as well as developing, economies.

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Cancer Gene Therapy Market Value to Hit $2.5 Billion by 2025: Global Market Insights, Inc. - PRNewswire

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When you have delayed onset of Alzheimers by three decades, you say wow, said Dr. Bu, chairman of the neuroscience department at the Mayo Clinic in Jacksonville, Fla., who was not involved in the study.

He said the research suggests that instead of drugs attacking amyloid or tau, which have failed in many clinical trials, a medication or gene therapy targeting APOE could be promising.

Dr. Reiman, who led another newly published study showing that APOE has a bigger effect on a persons risk of getting Alzheimers than previously thought, said potential treatments could try to reduce or even silence APOE activity in the brain. People born without APOE appear to have no cognitive problems, but they do have very high cholesterol that requires treatment.

Dr. Huang, who co-wrote a commentary about the study and is affiliated with two companies focusing on potential APOE-related treatments, said the findings also challenge a leading Alzheimers theory about the role of amyloid.

Since the woman had huge amounts of amyloid but few other Alzheimers indicators, it actually illustrates, to my knowledge for the first time, a very clear dissociation of amyloid accumulation from tau pathology, neurodegeneration and even cognitive decline, he said.

Dr. Lopera said the woman is just beginning to develop dementia, and he recently disclosed her genetic profile to her four adult children, who each have only one copy of the Christchurch mutation.

The researchers are also evaluating a few other members of the Colombian family, who appear to also have some resistance to Alzheimers. They are not as old as the woman, and they do not have the Christchurch mutation, but the team hopes to find other genetic factors from studying them and examine whether those factors operate along the same or different biological pathways, Dr. Reiman said.

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Why Didnt She Get Alzheimers? The Answer Could Hold a Key to Fighting the Disease - The New York Times

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These Five Life Science Organizations are Striving to Cure HIV

For those that lived through the devastation and horror of the HIV/AIDS epidemic of the early 1980s, effective treatment, let alone a cure for Human Immunodeficiency Virus (HIV), seemed unimaginable.

Some three decades later, a host of Maryland life science companies and research organizations are getting closer to making what was once unthinkable, real.

So little was known about this devastating immune disorder in the early phases of the HIV/AIDS epidemic.

In the early days of the HIV/AIDS crisis, the BioHealth Capital Region was the epicenter of HIV/AIDS research, with much of this groundbreaking research occurring within the lab of the now famed NIH researcher, Dr. Robert Gallo. In 1983 and 1984 Gallo and his collaborators co-discovered and confirmed that the virus responsible for the killer disease known as AIDS was human T lymphotropic virus type III (HTLV-III). Gallo and the company went on to develop the first test that identified the virus in humansthe HIV-antibody blood test.

By 1983 the disease had started to spread globally. By 1999, approximately 33 million people across the globe were living with HIV and an estimated 14,000,000 million people had died from AIDS since the epidemic began.

The 1995 approval of Highly Active Antiretroviral Treatment (HAART), which was the result of the remarkable, collaborative efforts of the scientific community, led to the reduction of AIDS-related deaths and hospitalizations by 60-80%. A short time later what was once a three-drug cocktail had been transformed into a pill taken once daily by HIV sufferers.

As of 2017, 19.5 million people are estimated to be receiving antiretroviral treatment globally. While one of the greatest achievements in medical history, HAART and subsequent treatment forms do not cure HIV. Within just weeks of stopping treatment, the virus returns to full strength and chronic inflammation caused by suppressed HIV can lead to adverse health effects over the long term. Current HIV treatments control it but do not cure it; in fact, research shows that those being treated for HIV are more susceptible to other diseases and health risks at an earlier age.

Despite the amazing advancements in HIV/AIDS treatments, HIV/AIDS continues to be a major global health threat.

It would be a fitting conclusion for an HIV cure to emerge from the state where the virus was first linked to AIDS and where the first human diagnostic was developed.

Multiple Maryland companies and research institutions are on the leading-age of HIV research and development, making the state a hotbed of potential next-generation HIV therapies and, possibly, the source of a cure for this devastating global health issue. Some of the most promising cure candidates are coming out of Marylands thriving cell and gene therapy cluster.

Lets take a look at some of the amazing progress thats happening right now across Maryland and take a deeper dive into five of the leading organizations that are on a mission to develop the first HIV cure.

AGT is a gene and cell therapy company with a proprietary gene-delivery platform to rapidly develop gene and cell therapies to cure infectious diseases, cancers and monogenic disorders.

One of its lead gene therapy products is a potential functional cure for HIV. AGT just announced that it has submitted the IND to the FDA for a Phase I trial of its autologous cell therapy for HIV.

While HIV has become a manageable chronic virus for many, in less developed countries HIV/AIDS is still a devastating illness. Developing an HIV cure would relieve millions from the side effects of antiretrovirals used to suppress HIV and prevent AIDS, avoid the serious quality-of-life issues of long-term treatment, and potentially save the lives of countless others.

AGT is currently developing a highly innovative HIV treatment strategy that uses the tools of genetic medicine for immunotherapy to potentially create a functional cure for HIV.

If we are successful, patients will be able to throw away their medication, will not progress to AIDS, and will be immune to future HIV exposures.

The potential single-dose treatment would be delivered as a genetically-modified cell product made from a patients own cells. AGTs strategy is unique because it focuses on the key immune cells responsible for catalyzing strong immunity against a virus. AGTs treatment strategy seeks to protect these cells; one of the first cell subsets to be disabled by HIV. This subset of cells is understood to be critical to building an immune response to any virus. If achieved, the cells natural process of immunity is restored and any future rise of HIV in the body will be attacked by an individuals own immune system.

AGTs treatment includes the production of an autologous cell product that is highly enriched for HIV-specific CD4+ T cells that are then transduced with a lentivirus vector known as AGT103 to protect against HIV-mediated T cell depletion. The combination of these enriched cells and the lentiviral vector forms a cell product AGT has dubbed AGT103-T. This cell product is delivered intravenously to HIV patients. AGT103-T should control viremia and work to remove infected cells from the body, thus eliminating the need for lifelong antiretroviral treatment.

AGT is currently collaborating with the Institute of Human Virology, University of Maryland Baltimore to collect leukapheresis specimens from HIV positive individuals for an ongoing observational study performing and qualifying the cell process, which is explained in greater detail here. The company expects its potential HIV cure to move into clinical trials in the next six months.

IHV is part of the University of Maryland School of Medicine and is a recognized leader in the virology field. IHV was founded by Dr. Robert C. Gallo who co-discovered HIV and developed the first HIV blood test.

IHV is heavily focused on HIV/AIDS research and the organization is currently progressing a promising HIV/AIDS vaccine through its pipeline. IHV01 (FLSC-001) has completed a Phase I trial and was supported, in part, from funding provided by the Bill and Melinda Gates Foundation.

This potential HIV/AIDS treatment seeks to neutralize the different strains of HIV found across the globe from the moment of infection. IHVs HIV/AIDS research is focused on the CCR5 chemokine receptor that plays a crucial role in HIV-1 infection and as such offers an important potential therapeutic target. (IHV Website). IHV is striving to develop biological HIV/AIDS treatments that are less expensive, have fewer adverse impacts and are more accessible to patients around the globe.

Lentigen is a leading provider of custom lentiviral vectors used in cell and gene therapy research and development. For HIV, Lentigen is at the forefront of efforts to use Chimeric Antigen Receptors (CAR) T-Cell therapy to improve the treatment of HIV and possibly cure it.

Lentigen, along with researchers at the University of Pittsburgh in Pennsylvania and the Albert Einstein School of Medicine, has been conducting a promising study of the use of CAR T in the treatment of HIV. The researchers developed duoCAR T cells that were able to kill white blood cells infected with a range of HIV variants. Testing in mice also produced promising results. Mice with humanized immune systems were simultaneously injected with CAR T cell and HIV-infected human cells into their spleens. When the spleens were examined a week later, five of the six mice had no identifiable HIV DNA and their viral levels had decreased by 97.5% (source: Science).

The study hopes to test the duoCAR T approach in HIV-infected people in the near future.

IBBR is a joint research enterprise of the University of Maryland, College Park and the National Institute of Standards and Technology (NIST). Last year IBBR received $3.9M from the National Institutes of Health (NIH) to develop a multi-specific, single-agent antibody therapeutic against HIV-1 to block virus infection and to clear the reservoir of HIV-infected cells from the body, according to an IBBR press release from November 2018.

The project is led by Dr. Yuxing Li, Associate Professor, Department of Microbiology and Immunology, University of Maryland School of Medicine, and Fellow at the Institute for Bioscience and Biotechnology Research (IBBR), in collaboration with Dr. Qingsheng Li, University of Nebraska-Lincoln, and Dr. Keith Reeves, Harvard Medical School/Beth Israel Deaconess Medical Center.

IBBRs research has focused on overcoming some of the limitations of existing antiretroviral (ARV) HIV treatments, including adverse side effects, ARV treatment drug resistance and how HIV integrates into the human genome, creating pockets of HIV that ARV cannot eliminate. Dr. Li and his group have produced bi and tri-specific antibodies that demonstrated neutralization of 95% of circulating HIV-1 viruses. These bi and tri-specific antibodies can also bind to multiple locations on the HIV-1 surface glycoprotein Env, which could potentially thwart treatment resistance via mutation. The team is now working to optimize their multivalent antibody constructs to recognize Env proteins on the surface of latently infected host cells, and to signal other immune system components to destroy those cells that contain the hard-to-reach viral pockets, or as the team calls them, a viral reservoir. (IBBR press release)

NIAID has been at the forefront of HIV research for decades and continues to be a major player in the research and development of possible HIV treatments and potential cures. NIAIDs research into HIV played a critical role in developing ARV drugs that transformed HIV into a chronic condition rather than a fatal infection.

NIAID-supported research has led to many ARV drug improvements, including reducing the number of pills required, diminishing adverse impacts and identifying the best drug combinations. The organization works with many leading global HIV/AIDS research organizations to identify and develop better HIV treatments.

NIAID is focused on both developing new HIV treatments as well as supporting other researchers and research organizations investigating new therapies. The ultimate goal is to potentially make HIV treatment a single dose, lifetime treatment, and, eventually, the complete eradication of HIV. NIAID is involved in many research and development projects focused on HIV and there are too many to dig into in a single article. Some of their current HIV research and development efforts are focused on investigational long-acting HIV drugs, rilpivirine LA and cabotegravir LA, for patients that have had difficulty following conventional antiretroviral therapy programs. Another NIAID study will test combining monthly injections of cabotegravir LA and infusions of an NIAID-discovered broadly neutralizing antibody called VRC01LS to see if the combination can keep HIV suppressed in people whose infection was previously controlled by antiretroviral therapy.

The organizations support has also helped in the discovery of the experimental drug islatravir (also known as EFdA or MK-8591) and maturation inhibitors. NIAID also has partnered with the Maryland industry, including a research collaboration agreement with AGT for research studies on the companys cell and gene therapy for HIV/AIDS.

A partnership between NIAID, Frederick National Labs for Cancer Research (operated by Leidos Biomedical Research, Inc.) and a team of collaborators recently developed 38 new simian/human immunodeficiency viruses (SHIVs) for prevention and treatment studies. These new SHIVs have closed a gap that previously existed in HIV research. These SHIVs are pathogens engineered in the lab that can help in the investigation of potential new HIV therapies as well as other treatments and vaccines.

These SHIVs target HIV subtype C, which causes approximately half of all HIV infections, and were created using HIV samples from people recently infected, allowing better modeling of more current forms of HIV subtype C circulating globally. The stronger modeling will increase pre-clinical researchs ability to predict effectiveness. Other SHIVs had used samples acquired from patients that had been infected long before the sample was pulled, limiting the SHIVs effectiveness against more current strains of HIV. While improvements are still needed, including challenges with replication, these new tools for HIV research and discovery hold tremendous promise.

In the late 1970s and early 1980s finding a cure for HIV/AIDS wasnt even on the radar. The scientific community was racing to understand the fundamentals of a virus that was rapidly spreading devastation and death across the globe. The speed with which the medical community came to understand the disease and to develop treatments like HAART is one of the truly amazing stories of the 20th century.

One or several of these Maryland companies and research institutions have a real chance to achieve what was once unthinkablefinding a cure for HIV that could help tens of millions of people across the globe live better, healthier and longer lives.

If an HIV cure emerges from Maryland, the BHCR community will have helped write the final chapter of HIV/AIDS terrible yet hopeful story.

Steve has over 20 years experience in copywriting, developing brand messaging and creating marketing strategies across a wide range of industries, including the biopharmaceutical, senior living, commercial real estate, IT and renewable energy sectors, among others. He is currently the Principal/Owner of StoryCore, a Frederick, Maryland-based content creation and execution consultancy focused on telling the unique stories of Maryland organizations.

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In the latest step toward development of potential treatments for Alzheimers disease, researchers have identified a rare gene mutation that seemingly prevented a Colombian woman from developing Alzheimers for decades.

Scientists said the research, published in the journal Nature Medicine, presents a tantalizing clue for why some people are resistant to developing Alzheimers.

Like many members of her extended family, the woman, from Medelln, Colombia, carried a gene mutation called presenilin 1. This gene is known to cause younger-onset Alzheimers. In fact, researchers said family members with the gene mutation have a 99.9 percent risk of developing the disease as early as their 30s.

However, the woman did not develop Alzheimers until her late 70s. Scientists suspect the disease was held at bay by another extremely rare gene mutation the woman had called APOE3 Christchurchor APOE3chnamed after Christchurch, New Zealand, where it was first identified.

Sometimes close analysis of a single case can lead to discovery that could have broad implications for the field, said Richard Hodes, Director of the National Institute on Aging (NIA), which provided funding for the research.

Dr. Guojun Bu, chairman of the neuroscience department at the Mayo Clinic in Jacksonville, FL, told The New York Times that the findings could be profound, although he stressed that much more additional research is needed.

When you have delayed onset of Alzheimers by three decades, you say wow, Bu said, adding that the research suggests a medication or gene therapy targeting APOE could be promising.

Yadong Huang, a neuroscientist at the Gladstone Institutes in San Francisco, called the case very special.

This may open up a very promising new avenue in both research and therapy, he told Science Magazine.

Neither Huang nor Bu were involved in the research, which was led by scientists at the Massachusetts General Hospital in Boston and the University of Antioquia in Medelln, Columbia, and the Banner Alzheimers Institute in Phoenix.

The NIA said that experiments undertaken as part of the study showed that the APOE3ch variant may inhibit the development of amyloid and tau protein deposits that destroy the brain.

Earlier this year, another set of researchers found that a gene linked to a rare neurological disorder may play a role in the development of Alzheimers.

For further background on genetic research and Alzheimers, watch a Being Patient video interview with Nathaniel Chin, Director of Medical Services at the Wisconsin Alzheimers Disease Research Center.

Link:
A Woman's High Risk of Developing Early-Onset Alzheimer's Was Delayed, Thanks to This Genetic Mutation - Being Patient

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PTC Therapeutics announced a strategic partnership with Aldevronto ensure the production of high-quality plasmid DNA to be used with PTCs investigational gene therapies, including AGIL-AS for the treatment of Angelman syndrome (AS).

PTCs growing gene therapy pipeline for genetic disorders of the central nervous system (CNS) also includes an investigational gene therapy for AADC deficiencythats nearing submission to the U.S. Food and Drug Administration (FDA), as well as candidates for Friedreichs ataxiaand Angelman syndrome that are at earlier development stages. Other candidates for cognitive disorders and inherited retinal disorders are in preclinical research.

Our strategic collaboration with Aldevron represents our continued commitment to produce and provide the highest quality product to patients, Neil Almstead, PhD, PTCs chief technical operations officer, said in a press release.

Our gene therapy pipeline is addressing the unmet needs of multiple patient populations, and we feel an urgent need to develop safe products with the utmost speed. The development of relationships with top-tier companies like Aldevron aligns with our goal of partnering with the best collaborators as we drive meaningful improvements in the lives of patients, Almstead said.

PTCs gene therapy candidate for Angelmans syndrome is called AGIL-AS. It uses a modified virus that does not cause infection called an adeno-associated virus (AAV) to deliver a working copy of the UBE3Agene, the faulty gene in Angelman syndrome, to the brain and spinal cord of patients. The process is designed to restore production of the E6-AP protein produced by the UBE3A gene, this way improving cell function and rescuing neurological defects in Angelman syndrome.

Preclinical studieshave shown that AGIL-AS targets nerve cells in the brain, increases levels of E6-AP, and eases AS-like cognitive deficits in animal models of the disease.

AGIL-AS was granted orphan drug designationfrom the U.S. Food and Drug Administration in 2015, followed by a similar designation from theEuropean Commission in 2016.

Under the agreement, Aldevron will manufacture the plasmid DNA (circular molecules of DNA) where the functional version of UBE3A gene will be enclosed for delivery. The company ensures the materials are produced under Good Manufacturing Practice (GMP), a set of guidelines allowing products to be consistently made and controlled according to quality standards.

It is truly an honor to work with PTCs motivated team of experts. They are making enormous contributions to the future of genetic medicine, saidMichael Chambers, founder and CEO of Aldevron.

This is Aldevrons mission to serve scientists and researchers who are relentlessly pursuing cures for people who need them, he added.

Ana is a molecular biologist enthusiastic about innovation and communication. In her role as a science writer she wishes to bring the advances in medical science and technology closer to the public, particularly to those most in need of them. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she focused her research on molecular biology, epigenetics and infectious diseases.

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Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

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SAN DIEGO, Nov. 5, 2019 /PRNewswire/ -- Poseida Therapeutics, Inc., a clinical-stage biopharmaceutical company leveraging proprietary non-viral gene engineering technologies to create life-saving therapeutics, today announced it will present preclinical research findings during the Society for Immunotherapy of Cancer (SITC)34th Annual Meeting on its lead allogeneic product candidate, P-BMCA-ALLO1, in multiple myeloma.

At SITC 2019, preclinical results will highlight the potential of Poseida's gene engineering technologies in addressing current challenges with earlier generation autologous CAR-T therapies. Poseida leverages its proprietary piggyBac DNA Modification System in combination with Cas-CLOVER gene editing technology to create P-BCMA-ALLO1, an off-the-shelf allogeneic CAR-T cell product candidate. These technologies enable the development of allogeneic CAR-T therapies with a variety of benefits to patients and the medical community including greater safety and duration of response, as well as manufacturing and patient cost savings.

Poseida will present the following research at SITC 2019:

"Broad adoption of earlier generation CAR-T therapies have been curtailed by serious safety concerns, limited duration of response and difficulty supporting access within the current healthcare system," said Eric Ostertag, M.D., Ph.D., chief executive officer of Poseida. "We are actively problem-solving to address these challenges and our new findings indicate that we are making progress with our allogeneic approach powered by our piggyBac DNA Modification System and Cas-CLOVER gene editing technology."

About P-BCMA-ALLO1P-BCMA-ALLO1 is an allogeneic CAR-T therapy being developed by Poseida for multiple myeloma. It is designed to have the benefits of scale and administration efficiency that come from an allogeneic product. Poseida expects to file an IND for P-BCMA-ALLO1 in 2020. Approximately 32,110 people were diagnosed with multiple myeloma and 12,960 died from the condition in the United States in 2019.

Click to Tweet: Poseida Therapeutics to Present Update on Approach in Allogeneic CAR-T at Society for Immunotherapy of Cancer 34th Annual Meeting #celltherapy #genetherapy

About Poseida Therapeutics, Inc.Poseida Therapeutics is a clinical-stage biotechnology company translating best-in-class technology into lifesaving cell and gene therapies for patients with high unmet medical need. The company is developing a wholly-owned pipeline of non-viral, allogeneic and autologous CAR-T product candidates and in vivo gene therapies for orphan genetic diseases. Poseida has assembled a suite of industry-leading gene editing technologies, including the piggyBacDNA Modification System and Cas-CLOVER and TAL-CLOVER site-specific nucleases. For more information, visitwww.poseida.com.

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Collaboration Includes Exclusive Rights and Targets for Initial Applications in Non-Hodgkin Lymphoma, Leukemia and Multiple Myeloma

Notch to Receive Upfront Payment, Research Funding and an Equity Investment Plus Development and Commercial Milestones and Royalties on Net Sales

SOUTH SAN FRANCISCO, Calif. and TORONTO, Nov. 05, 2019 (GLOBE NEWSWIRE) -- Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) therapies for cancer, and Notch Therapeutics Inc., an immune cell therapy company creating universally compatible, allogeneic T cell therapies for the treatment of diseases of high unmet need, today announced an exclusive worldwide collaboration and license agreement to research and develop induced pluripotent stem cell (iPSC) AlloCAR therapy products for initial application in non-Hodgkin lymphoma, leukemia and multiple myeloma. Under the partnership, Allogene and Notch will create allogeneic cell therapy candidates from T cells or natural killer (NK) cells using Notchs Engineered Thymic Niche (ETN) platform.

Notch was established in 2018 by Juan Carlos Ziga-Pflcker, Ph.D. and Peter Zandstra, Ph.D., recognized pioneers in iPSC and T cell differentiation technology. Notch is developing a next-generation approach to differentiating mature immune cells from iPSCs. The Notch ETN technology platform offers potential flexibility and scalability for the production of stem cell-derived immune cell therapies. iPSCs may provide renewable starting material for AlloCAR T therapies that could allow for improved efficiency of gene editing, greater scalability of supply, product homogeneity and more streamlined manufacturing.

This collaboration exemplifies Allogenes long-term commitment to advancing the field of cancer treatment as we continue to expand and progress our innovative pipeline of off-the-shelf AlloCAR candidates, said David Chang, M.D., Ph.D., President, CEO and Co-Founder of Allogene Therapeutics. The scientific founders of Notch Therapeutics are among the most respected experts in the field of stem cell biology and its applications to generating T cells and other functional immune cells. We are confident that their technology and expertise, combined with Allogenes leadership in AlloCAR therapies, has the potential to unlock future generations of cell therapy treatments for patients.

Renewable-source, off-the-shelf cell therapies that may produce cells with greater consistency and at industrial scale have long been the dream for people working in this field, said Ulrik Nielsen, Ph.D., Executive Chairman of Notch. We are delighted to spring into the research collaboration for iPSC-based AlloCAR therapies with Allogene, a leader in the allogeneic CAR T field, with the goal of expanding options for patients.

Under the terms of the agreement, Notch will be responsible for preclinical research of next-generation iPSC AlloCAR T cells. Allogene will clinically develop the product candidates and holds exclusive worldwide rights to commercialize resulting products. Allogene will provide to Notch an upfront payment of $10 million. Notch will be eligible to receive up to $7.25 million upon achieving certain agreed research milestones, up to $4.0 million per exclusive target upon achieving certain pre-clinical development milestones, and up to $283 million per exclusive target and cell type upon achieving certain clinical, regulatory and commercial milestones as well as tiered royalties on net sales in the mid to high single digits. In addition to this collaboration and license agreement, Allogene has acquired a 25 percent equity position in Notch and will assume a seat on Notchs Board of Directors.

Master cell banks of genetically modified, induced pluripotent stem cells could provide an inexhaustible source of cell therapies that may improve outcomes and expand applicability to new areas, said Notch Co-Founder Juan Carlos Ziga-Pflcker, Ph.D., a senior scientist at Sunnybrook Research Institute and a Professor and Chair of the Department of Immunology at the University of Toronto.

This work with Allogene may also pave the way for additional off-the-shelf cell therapeutics that are custom-designed to treat other immunity-related diseases such as infectious diseases, autoimmune diseases and aging, said Notch Co-Founder and Chief Scientific Officer Peter Zandstra, Ph.D., a Professor at the University of British Columbia and University of Toronto.

About Notch Therapeutics (www.notchtx.com)Notch is an immune cell therapy company creating universally compatible, allogeneic (off-the-shelf) T cell therapies for the treatment of diseases of high unmet medical need. Notchs technology platform uses genetically tailored stem cells as a renewable source for creating allogeneic T cell therapies that expand treatment options and deliver safer, consistently manufactured and more cost-effective cell immunotherapies to patients. At the core of Notchs technology is the synthetic Engineered Thymic Niche (ETN) platform, which drives the expansion and differentiation of stem cells in scalable, fully defined, feeder-free and serum-free cultures into T cells that can be genetically tailored for any T cell-based immunotherapeutic application. This technology was invented in the laboratories of Juan-Carlos Ziga-Pflcker, Ph.D. at Sunnybrook Research Institute and Peter Zandstra, Ph.D., FRSC at the University of Toronto. Notch was founded by these two institutions, in conjunction with MaRS Innovation (now Toronto Innovation Acceleration Partners) and the Center for Commercialization of Regenerative Medicine (CCRM) in Toronto.

About Allogene TherapeuticsAllogene Therapeutics, with headquarters inSouth San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor Tcell (AlloCAR T) therapies for cancer. Led by a world-class management team with significantexperience in cell therapy, Allogene is developing a pipeline of off-the-shelf CAR T cell therapycandidates with the goal of delivering readily available cell therapy on-demand, more reliably, and atgreater scale to more patients. For more information, please visitwww.allogene.com, and follow @AllogeneTx on Twitter and LinkedIn.

Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as "predicts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the ability to progress the research collaboration, Notchs ability to develop a next-generation approach to differentiating mature immune cells from iPSCs, the ability to develop and manufacture new therapies from Notch technology, and the potential benefits of Notch technology and AlloCAR T therapy. Various factors may cause differences between Allogenes expectations and actual results as discussed in greater detail in Allogenes filings with theSecurities and Exchange Commission(SEC), including without limitation in its Form 10-Q for the quarter endedJune 30, 2019. Any forward-looking statements that are made in this press release speak only as of the date of this press release. Allogene assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

Allogene Media/Investor Contact:Christine CassianoChief Communications Officer(714) 552-0326Christine.Cassiano@allogene.com

Notch Media Contact:Mary MoynihanM2Friend Biocommunications802-951-9600mary@m2friend.com

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These platforms include the proprietary ShapeTx RNAfix technology that enables direct in vivo targeting and modification of RNA by leveraging proteins such as Adenosine Deaminases Acting on RNA (ADARs), suppressor tRNAs, and engineered adeno-associated viruses (AAVs). The RNAfix platform differentiates from other contemporary genome engineering technologies by engaging natural human cellular machinery to modify RNA.

ShapeTx was founded on the work of Dr. Prashant Mali, Assistant Professor of Bioengineering at UCSD, who during his postdoctoral fellowship in the George Church laboratory at Harvard Medical School pioneered the use of CRISPR in human cells. ShapeTx RNAfix platform is built upon his lab's most recent work demonstrating in vivo use of guide RNAs to recruit native ADARs and to fix mutations in multiple rare genetic disease mouse models.

Our technology can correct mutations or target specific genes in neurodegenerative, oncology, metabolic and rare genetic disorders by hijacking naturally occurring proteins such as ADARs present in our cells using just a short guide RNA. Our proprietary new platform avoids the risk of in vivo immunogenicity and permanent off-target damages commonly associated with CRISPR-based approaches, explained Francois Vigneault, Ph.D., President and CEO, who was previously VP of Research at Juno Therapeutics after a successful co-acquisition of AbVitro, Inc. by Juno and Celgene.

Ed Mathers, Partner at NEA and Board member at ShapeTx, said, One rarely comes across a proprietary technology platform with such transformative potential led by a focused and data-driven scientific group with a successful track record in pre-clinical and clinical development. The team has shown us an exciting demonstration of the technology in multiple in vivo models, alongside one of the strongest IP estates we have seen in the field. NEA looks forward to backing the company in future rounds as they move the technology toward the clinic.

While the ShapeTx platform will be enabling for many other genetic diseases, Dr. Malis in vivo proof of concept in Duchenne Muscular Dystrophy was quite exciting and could potentially lead to a cure for families suffering from such a debilitating disorder, said Debra Miller, CEO and Founder of CureDuchenne and CureDuchenne Ventures.

The ShapeTx Series A financing coincides with the formation of a world-class Scientific Advisory Board comprised of foremost global experts in genomics, bioengineering, and gene editing, including George Church Ph.D., James Collins Ph.D., and Don Cleveland Ph.D. The scientific advisory board will serve as strategic advisors and ensure that the research and development of its platforms meet the highest standards of scientific merit.

Prashant and Francois are some of the most innovative and brilliant individuals that have come through my lab over the years, and it will be impressive to see these two disrupt the field of gene therapy with this paradigm-shifting technology, said Dr. George Church, Professor in Genetics at Harvard Medical School and member of the ShapeTx Scientific Advisory board.

Shape Therapeutics Scientific Advisory Board Members:

George Church, Ph.D.

George Church Ph.D., world-famous geneticist, molecular engineer, and chemist. He developed the methods used for the first genome sequence & million-fold cost reductions since, as well as pioneered many of the CRISPR advances in genome editing. He is currently a Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard and the Massachusetts Institute of Technology (MIT). He is Director of the U.S. Department of Energy Technology Center and Director of the National Institutes of Health Center of Excellence in Genomic Science. He has received numerous awards, including the 2011 Bower Award and Prize for Achievement in Science from the Franklin Institute and election to the National Academy of Sciences and Engineering.

James Collins, Ph.D.

James Collins Ph.D., is one of the pioneers of the field of synthetic biology and has made multiple synthetic biology and bioengineering breakthroughs in biotechnology and biomedicine. He serves as the Termeer Professor of Medical Engineering & Science and Professor of Biological Engineering at MIT, as well as a member of the Harvard-MIT Health Sciences & Technology Faculty, and core member of the Wyss Institute. His many awards include a Rhodes Scholarship, a MacArthur Genius Award, a National Institutes of Health Directors Pioneer Award. Jim is also an elected member of the National Academy of Sciences, the National Academy of Engineering, the National Academy of Medicine, the American Academy of Arts & Sciences, as well as a charter fellow of the National Academy of Inventors.

Don Cleveland Ph.D.

Don Cleveland Ph.D. is an award-winning inventor and pioneer in the field of Antisense Oligonucleotide (ASO) and their uses in gene therapy. He was recently awarded the Breakthrough Prize in Life Sciences for his work on the pathogenesis of disease and ASO-mediated treatment approaches in ALS and Huntingtons disease. Don is currently Professor of Medicine and Department Chair of Cellular and Molecular Medicine and Neurosciences at the University of California at San Diego, and Head, Laboratory for Cell Biology at the San Diego branch of Ludwig Cancer Research. He has made pioneering discoveries on the mechanisms of chromosome movement and cell-cycle control during normal cellular division, as well as the principles of neuronal cell development and the relationship to defects that contribute to inherited neurodegenerative disease.

About Shape Therapeutics, Inc.

Shape Therapeutics, Inc. is creating the worlds leading RNA and protein targeting platforms focused on the cure of human diseases. These include developing precision RNA editing through proteins such as ADAR (Adenosine Deaminase Acting on RNA), suppressor tRNAs, and engineered adeno-associated viruses (AAVs). The RNAfix technology allows for the editing of RNA using natural human cellular machinery, limiting the risk associated with immunogenicity, cellular toxicity, or off-target DNA editing. The teams founders include Prashant Mali, Ph.D., Francois Vigneault, Ph.D., and John Suliman. ShapeTx is headquartered in Seattle, Washington, with a satellite site opening in Cambridge, Massachusetts. For additional information, visit http://www.ShapeTx.com.

About NEA

New Enterprise Associates, Inc. (NEA) is a global venture capital firm focused on helping entrepreneurs build transformational businesses across multiple stages, sectors, and geographies. With more than $20 billion in cumulative committed capital since the firm's founding in 1978, NEA invests in technology and healthcare companies at all stages in a company's lifecycle, from seed stage through IPO. The firm's long track record of successful investing includes more than 225 portfolio company IPOs and more than 375 acquisitions. For additional information, visit http://www.nea.com.

About CureDuchenne Ventures

CureDuchenne Ventures supports Duchenne research by using philanthropic donations to encourage the development of new Duchenne drugs. Through an impact financing model, we can provide equity or royalty financing to biotech and pharmaceutical companies. CureDuchennes portfolio includes 16 wide-ranging projects with several successful exits. Investments from CureDuchenne Ventures have successfully de-risked and leveraged more than $2.3 billion in follow-on financing from venture capital, biotech, and pharmaceutical companies to fund emerging projects to find treatments for Duchenne. For additional information, visit https://www.cureduchenne.org/ventures/.

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Shape Therapeutics, Inc. Raises $35.5M Series A Financing, Led by NEA and Announces the Formation of a World-Class Scientific Advisory Board, to...

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