Category Archives: Genetic Therapy

CAR-T cells that have been so successful against some leukemias and lymphomas often cause a violent and even life-threatening immune reaction.

The problem, the researchersreportedon [January 17], is that CAR-Ts attack and kill cancer cells in the messiest way biologists have ever seen.

That violent cell death, called pyroptosis, is the first step down the biological road that ends in the immune storm, he and his colleagues showed in human cancer cells growing in lab dishes as well as injected into mice and treated with CAR-Ts.

In addition to identifying the molecular steps that start with this violent cell death and end with the immune overreaction, or cytokine release syndrome (CRS), [immunologist Bo] Huang and his colleagues discovered a possible way to prevent it.

Tweaking the receptor on CAR-T cells that recognize cancer cells seemed promising, but made the CAR-Ts less effective against cancer cells. A more effective approach, at least in mice, was to block the molecules that make tumor cells die via pyroptosis rather than less violently. That should not affect [cancer-]killing efficacy, Huang said, but can prevent cytokine release syndrome.

Read the original post here

Read the original post:
Refining CAR-T therapy could halt 'violent, life-threatening' immune reactions - Genetic Literacy Project

Investment Thesis

Precision Biosciences (NASDAQ:DTIL) is a biotech company with a proprietary gene-editing platform - ARCUS - 15 years in the making, and a promising genome editing endonuclease - I-CreI - an enzyme naturally occurring in a type of algae.

The stock currently trades at $11. Consensus amongst analysts suggests that the current price undervalues the company slightly. 1-year Price targets set by 6 firms are between $21 and $24 (Source: "CNN").

The company has a strong cash position ($206m as at Q319) plus development and commercial partners in place poised to reward development of lead drug candidates PBCAR0191 ("CD19", a CAR-T therapy targeting non-Hodgkin's Lymphoma) and HBV (an in vivo gene correction therapy targeting Hepatitis B).

The third string to Precision's bow is Elo Life Systems, which uses the Arcus platform to develop promising solutions targeting genetic engineering of foods including Canola oil, watermelon, and chickpeas.

Below, I present an overview of the company and analysis of the progress of the three business divisions, based around the IPO prospectus, a recent corporate presentation (Source: Seeking Alpha) delivered at the JP Morgan Annual Health Conference, and early results from clinical trials of allogeneic, or "off-the-shelf" CAR-T treatment PBCAR0191.

In my view, Precision has excelled on the business, sales, and marketing front. Besides the IPO and commercial deals, a brand new, 17,300 square foot in-house cGMP clinical manufacturing facility - the Manufacturing Centre for Advanced Therapeutics ("MCAT") - is production-ready.

On the drug development/gene editing side of the business, however, I am not convinced that Precision's progress since its IPO has been sufficient to justify a "buy" rating on this stock. After reviewing the JPM presentation in detail personally, I do not think there is enough reported progress for investors to get excited about. I will go into more detail below, but to summarise:

As such, I have concerns about whether Precision can deliver any value for investors over the short, medium or long term. Some may argue that it is unrealistic to expect rapid progress, given the relatively short time since Precision went public. Others may feel that management's proven ability to sell the promise of its product and raise funds is more important (and better for the share price) than delivering tangible results at this stage.

A positive set of trial results could rapidly progress a drug candidate towards approval and commercialisation and send the stock price surging, but I think this is unlikely. Precision's next primary completion date for PBCAR0191 - its best candidate - will arrive in July, with a progress updates expected this quarter.

I struggle to see value in the ARCUS platform, or how the company will collect its milestone payments based on its current pipeline. If the company has to seek funding via an alternative route, it would likely be at a significantly reduced share price. With a cash burn of $81m in the first 9 months of 2019, this could cause Precision real problems, which would be compounded still further if its partners do not take up options on further development drugs.

There are positives such as the manufacturing facility - which could be repurposed if the drug candidates fail - the promise of CAR-T in general, and the huge addressable market that genetically modified food may present - albeit most likely many years down the line, if ever.

On balance, however, I believe investors are more likely to see the stock fall back below $6 on a lack of positive news flow and face a long wait for meaningful signs there is any real value in this company's product pipeline.

Precision BioSciences' proprietary drug-development platform ARCUS uses numerous protein engineering methods designed in-house to re-program the DNA recognition properties of an enzyme/endonuclease called I-CreI. I-CreI occurs naturally in an alga known Chlamydomonas reinhardtii. (Source: Precision Biotechnologies IPO prospectus)

Precision is developing product candidates across three distinct areas: allogeneic CAR T immunotherapy, in vivo gene correction, and food production.

In order to edit a genome, a DNA cutting enzyme known as an endonuclease is delivered to a pre-targeted section of genetic code. The endonuclease cuts into the DNA, which causes the cell to repair itself in order to survive.

The cell does this in one of two ways. The first is by a method known as non-homologous end joining ("NHEJ"). The DNA is repaired, but without following a specific template. This makes the repair speedier but usually causes the gene's function to be "knocked out" - rendered inactive.

An alternative method is referred to as homology directed repair (HDR). This method uses a second DNA molecule as a template to guide the repair process. The new DNA is hard-coded using the template, meaning a new gene can be "knocked in" in a precise location, or the existing gene repaired.

In its natural state I-CreI modifies a specific location in the algae's genome using HDR. Precision believes that because I-CreI is used to operating with larger and more complex genomes, it may be optimally suited to making edits to a human genome.

How I-CreI works. Source: Precision BioSciences Presentation at 38th Annual JP Morgan Healthcare Conference Jan. 2020

Management's view is that I-CreI presents 4 key advantages over the rival endonuclease-based solutions being developed by its rivals.

Due to its complexity, I-CreI presents a tougher engineering challenge relative to other endonucleases. Precision management argues this makes I-CreI a superior, more valuable product which presents high barriers to entry to rival drug developers. Precision has been developing its I-CreI-focused ARCUS platform for 15 years and has secured numerous intellectual property rights.

The promise of Precision's "allogeneic" CAR-T immunotherapy drug candidate PBCAR0191 ("CD19") was the main reason for a recent uplift in the company's share price from a post-IPO low of $6.44 at the end of November to a post-IPO high of $20 in early December.

CAR-T cell therapy is an indication for cancer patients that have not responded to traditional treatments. The most common form of CAR-T - "autologous" - involves removing T-cells from a patient's own immune system, re-engineering them to express a protein known as a chimeric antigen receptor ("CAR"), and then re-injecting the modified T-cells back into the patient.

The re-engineered T-cells are able to identify and kill tumor cells that would otherwise avoid detection by T-cell receptors ("TCRs") that are expressed on the surface of T-cells. The re-injected T-cells are able to bypass these TCRs.

2 autologous treatments - axicabtagene ciloleucel (brand name Yescarta, owned by Gilead (NASDAQ:GILD), list price $375,000) and Tisagenlecleucel (brand name Kymriah, owned by Novartis (NYSE:NVS), list price $475,000) have now been approved by the FDA. (Source: "AJMC").

Autologous treatment has several drawbacks, however.

If a patient's T-cells are not of sufficient quality, for example, harvesting them (a process known as leukapheresis) becomes too risky. Overall, extracting, re-engineering, and re-injecting T-cells into patients can be slow, costly, and potentially unsafe.

Precision is one of several companies (others include CRISPR Therapeutics (CRSP), Sangamo Therapeutics (SGMO) and Intellia Therapeutics (NTLA) pioneering the use of "allogeneic", or donor-derived CAR-T therapy, extracting healthy T-cells from qualifying donors rather than the target patient. It is hoped that this form of "off the shelf" treatment could significantly speed up the CAR-T process and deliver a better health outcome for the patient.

Precision believes that they can re-engineer T-cells from donors at scale, making the process cheaper without sacrificing (and hopefully improving) the quality of the treatment.

Allogeneic CAR T vs Autologous CAR T. Source: Source: Precision IPO Prospectus

The company's one-step ARCUS engineering process could both "knock out" the gene that encodes TCR (avoiding the risk of a condition known as graft vs. host disease whereby newly introduced cells indiscriminately attack unintended targets) and "knock in" a gene containing CAR which can target and kill tumorous cells.

How the one-step engineering process works: Source: Precision IPO Prospectus

Precision Product Candidates for CAR T Immunotherapy. Source: Precision Website

In March 2019, Precision initiated dosing for CD19 in a Phase 1/2a clinical trial in adult patients with relapsed or refractory ("R/R") non-Hodgkin lymphoma ("NHL") or R/R B-cell precursor acute lymphoblastic leukemia ("B-ALL"). The trial - scheduled to complete in June 2021 with preliminary results due in July this year - is designed to test safety and tolerability at increasing dose levels with a secondary observation being to evaluate for signs of anti-tumor activity.

Some preliminary results from the trial, published in November (Source: Globenewswire) triggered a 157% uplift in Precision's share price (from $7 to $18) pushing Precision above its IPO price for the first time.

Three patients with advanced NHL were treated with CD19 at dose level 1 (3.0 x 10^5 cells/kg) with no significant toxicities observed. Two of the three patients experienced an objective tumor response based on Lugano criteria. The third patient (who had already received the CAR T autologous treatment Yescarta) did not meet the definition of response but showed signs of reduced tumor size.

A further update in December (Source: Seeking Alpha) announced at the annual meeting of the American Society of Hematology initially seemed to impress investors - driving the share price above $20 for the first time - before a sharp selloff sent the stock back below $10.

The data concerned 9 patients, 6 being treated for NHL - 3 at DL 1 and 3 at DL 2 (1.0 x 10^6 cells/kg) - and 3 for B-ALL (all being treated at DL 2).

Regarding the primary endpoint of the trial, safety, no serious adverse events ("SAE"s) were reported. Three patients developed cytokine release syndrome ("CRS") - an inflammatory reaction to infusion which can lead to Graft vs Host disease - 2 at grade 1 level and 1 at grade 2 level. Another patient developed grade 2 neurotoxicity, whilst another experienced a grade 3 adverse event ("AE") and another grade 4 lymphopenia - a reduction in white blood cells known as leukocytes.

In terms of best response at 28 days, the NHL cohort results showed a 67% objective response rate with 3 partial responses and 1 complete response, whilst the B-ALL cohort showed 1 complete response.

How does this compare with Yescarta/Kymriah? According to Precision data, in similar trials involving NHL patients, Yescarta achieved a 54% CRR and 82% ORR with 13% of patients reporting grade 3/4 CRS and 28% grade 3/4 Neurotox - a side-effect of chemotherapy which can be life-threatening above grade 4 level.

Also for NHL, Kymriah reported 40% CRR and 53% ORR with 18% of patients reporting Grade 3/4 CRS and 12% grade 3/4 neurotox.

CD19 Phase 1/2a reported trial results for NHL. (Source: Precision Presentation at JPM Healthcare conference Jan '20).

Concerning the B-ALL cohort, CD19 results showed a 33% CRR compared to Yescarta's 68% and Kymriah's 60%.

CD19 Phase 1/2a reported trial results for ALL. (Source: Precision Presentation at JPM Healthcare conference Jan '20).

Precision say that once dosage levels ("DL") are increased to comparable levels CD19 results will match or exceed the autologous solutions Kymriah and Yescarta.

CD19 Dose levels compared to Autologous CAR T products: (Source: Precision Presentation at JPM Healthcare conference Jan '20).

But it is important to note that increasing the dose may mean that safety issues also escalate - an issue that investors picked up on. The trial continues with treatment of patients at DL 3 and preliminary results due out this quarter will therefore be important.

What seemed most troublesome about the recent results was the fact that several patients relapsed. Durability of response is one of the key factors that Precision will be judged upon. One of the NHL cohort patients (treated at DL1) who had relapsed after treatment with Yescarta achieved a partial response, but eventually relapsed after 6 months. This was the longest partial response to date.

Two other NHL patients treated with DL1 and DL2, respectively, achieved early (after 14 day) responses but showed signs of disease progression after 28 days. Only 1 patient (treated at DL2) remains in complete response.

In the B-ALL cohort, 2 patients did not achieve a response whilst the third achieved a partial response and continues to be monitored. The 2 non-responders had poor prognostic indicators upon entry into the trial, one with 95% blast infiltration into the bone marrow, and one with 77%.

Precision's Chief Medical Officer Chris Heery commented on the results:

These data give us incremental confidence in our unique approach to allogeneic CAR T cell therapy, and we look forward to the potential of this therapy positively impacting the lives of more patients as the trial continues. At these still low dose levels, and using only mild lymphodepletion, it is remarkable to see anti-tumor activity in the majority of patients treated with PBCAR0191.

The investment community, however, did not seem to share his enthusiasm. Concerns over durability and safety and a lack of persuasive evidence that CD19 can deliver better outcomes than the CAR-T therapies already on the market created a sell-off.

Precision has a lot riding on its ability to deliver promising drug candidates for CAR-T therapy having secured a potentially lucrative deal with French pharmaceutical Servier Laboratories. By the terms of the agreement, Precision has agreed to develop allogeneic CAR T cell therapies for up to six unique antigen targets selected by Servier over the next four years, and to progress them through clinical trials.

Precision has received an upfront payment of $105m under this agreement (the first candidate being PBCAR0191). The company stands to earn up to $401.3m in milestone payments for progressing each candidate through clinical trials, and up to $1.1bn in commercial milestone payments should the drug candidates receive FDA approval for commercialisation. Precision would then receive tiered royalties between mid-single digit and low-teen percentages from Servier's global commercial sales of the approved product.

Besides CD19, the FDA has also accepted an investigational new drug (IND) application for Precision's second candidate, PBCAR20A ("CD20"). In this case, Precision are going it alone as this candidate is not part of the Servier agreement.

As the name suggests, the drug targets tumor cell surface target CD20. Both CD19 and CD20 are membrane-embedded surface molecules which play a role in the development and differentiation of B-cells into plasma cells. Rituximab, a chimeric monoclonal antibody against CD20, was first approved in 1997 and is now on the World Health Organisation's list of essential medicines (Source: Wikipedia).

A Phase 1/2 trial of CD20 to determine an optimal dose and evaluate clinical activity in subjects with relapsed/refractory ("r/r") NHL or r/r chronic lymphocytic leukemia ("CLL") began in October last year with preliminary results due in May 2020 and the study due to complete in February 2021.

Similar to the CAR-T development deal with Servier, Precision has an agreement in place with Gilead Sciences to develop genome editing tools using ARCUS targeting viral DNA associated with the Hepatitis B virus. The company has granted Gilead permission to develop and commercialise Precision's synthetic nucleases in exchange for $40m of research funding over the next 3 years, plus milestone payments worth up to $105m in development, $340m in commercial milestone payments, and tiered royalty payments on worldwide net sales.

Precision's "In Vivo" Gene Correction Pipeline. (Source: Precision Presentation at JPM Healthcare conference Jan '20).

Precision/Gilead's lead candidate "HBV" targets chronic Hepatitis B infection. Management says they will submit an Investigational New Drug Application ("IND") to the FDA sometime in 2020 (Source: Precision IPO Submission).

Other drugs currently in the discovery pipeline target indications, including familial amyloid polyneuropathy, primary hyperoxaluria, hemophilia A, retinitis pigmentosa, lipoprotein lipase deficiency, and familial hypercholesterolemia.

HA01, another candidate not subject to outside research funding or milestone payments targets primary hyperoxaluria, a rare genetic disease caused by loss-of-function mutations in the ACXT gene that affects 1-3 people in every million. Suppression of HA01 prevents the formation of oxalate which causes painful and potentially fatal kidney stones.

Precision subsidiary ELO Life Systems addresses a "human health opportunity" based around climate change concerns and growing consumer preference for healthier diets.

This segment has its own dedicated management team and intends to use ARCUS genome sequencing and functional genomics to develop early stage development programs that will be primarily partner-driven.

ARCUS-driven Food Pipeline. (Source: Precision Presentation at JPM Healthcare conference Jan '20).

To date, ELO has initiated a low saturate Canola Oil program in partnership with Cargill, and a proprietary "Zero Melon" program that activates dormant genes in the fruit to produce a sweetener that is similar to cane sugar. Management says that the global food sweetener market will be worth $82bn by 2024 and hopes to complete greenhouse trials in 2021 and begin large scale multi-site trials in 2023 with a view to releasing a commercial product within 4-5 years.

Precision Income Statement. Source Q319 10Q Submission.

Milestone payments and research grants aside, Precision is unlikely to become revenue generating in the foreseeable future.

The company has a relatively healthy cash position of $206.2m. Based on its reported Q319 R&D and G&A expenses of $26.8m (and $81m for the first 9 months of 2019), this should be enough to see the company through to the end of 2021 without the need to dilute investors with a stock offering or seek a further loan agreement. Precision has secured a revolving line of credit with Pacific Western bank worth up to $50m, which expires in May 2022.

Precision does not discuss the total addressable market ("TAM") for its products or make any sales forecasts across any of its 3 business lines either in its IPO prospectus or financial statements, which is likely due to the early stage nature of its various programs.

Concerning Allogeneic CAR-T, for guidance, we can look at the sales revenues of the two approved CAR-T treatments - Yescarta and Kymriah - plus the NHL market as a whole.

Gilead-owned Yescarta achieved global Q319 sales revenues of $118m (Source: Gilead 10Q Q319) - a year-on-year increase of 57%. $86m of sales were made in the US and $32m in Europe. Novartis-owned Kymriah secured sales of $79m over the same period, up 295% year-on-year (Source: Novartis interim financials Q319).

Sales of both have disappointed analysts who expected more from a breakthrough immunology therapy. A decision by the Centers For Medicare and Medicaid Services ("CMS") in August last year, however - that Medicare will pay for CAR-T therapies, provided they are administered at certified health facilities and as part of a Risk Evaluation and Mitigation Strategies ("REMS") - may pave the way for increased adoption of CAR-T focused therapies.

Consensus estimates have forecast Yescarta's 2022 sales revenues to be as high as $1.7bn, and Kymriah's as high as $994m. (Source: Evaluate). By my calculations, this represents a CAGR for combined revenues of 58%.

A best-case scenario for Precision's CAR-T division up to 2025 therefore may look something like this.

The market for treatment of non-Hodgkin's lymphoma as a whole has been estimated to reach $9.2bn by 2020 at a CAGR of 7.4% (Source: ReportsnReports.com). If we extrapolate these numbers out to 2025, the TAM for NHL would be $12.2bn. If we assume CAGR of Yescarta and Kymriah sales to be a more modest 19% between 2023 and 2025, then we have a scenario where sales of both combined could reach $3.8bn in 2025. CAR-T treatment would then account for ~31% of the total estimated treatment market for NHL.

If we assume that CD19 is granted approval in 2022 and claims a further ~4% of the total NHL treatment market (meaning CAR-T represents 35% of total NHL market) by 2025, then total sales could amount to ~$461m.

CD19 - the first of 6 candidates to be developed under the Servier agreement could earn one-sixth of the total $1.6bn milestone payments on offer - $227m - for negotiating all trials and achieving commercialisation. As part of the revenue-sharing agreement, Precision could earn ~$55m in annual sales revenues from its agreement with Servier (based on the above calculations and assuming a 12.5% share of all sales).

Then, there is CD20, which does not qualify for any milestone payments, but Precision earns 100% of sales. It would be interesting to see what happens if both treatments were approved as surely there would be a conflict of interest if both drugs were addressing the same target market. Surely, Precision would favour CD20?

Given the speculative nature of this scenario, I will go no further into my financial model for now, but hopefully, this will give investors some additional insight into the kinds of revenues that Precision could potentially generate. My view is that there may be some doubt around whether Precision can generate significant enough sales revenues to support its ongoing R&D, manufacturing and distribution costs. Thus, even in a best-case scenario, it's hard to make a bull-case for Precision, in my view.

According to a report from Prescient & Strategic Intelligence, the global market for hepatitis drugs is expected to reach $118.5bn by 2020 at a CAGR of 29.7% from 2015. Whether Precision can penetrate this market in the face of strong competition is too early to say. Additionally, the rewards on offer from its commercial partner Gilead are not as substantial as those provided by Servier. Just $40m toward development and milestone payments of up to $105m for development and $340m for commercialisation. Whilst the addressable market is huge, Precision will only receive tiered royalties, and its treatments may only address a small niche of the overall market since its candidates are unlikely to become first or even second line therapies.

I briefly addressed the food market above, but again, Precision expects partners to assume most of the responsibility - and presumably revenues - from the projects it helps to develop. This market is also highly speculative in nature since nobody really knows whether genetic editing of food would work in practice or whether better solutions will emerge.

Precision is a company with bold ambitions. Their presentation talks about overcoming cancer, curing genetic disease and feeding the planet, but in reality, the company is a long way from even being close to solving any of these issues.

The main concerns I would have regarding Precision would be as follows:

There are also some reasons to paint a more optimistic picture.

Overall, I would reiterate that I am somewhat bearish on Precision. I have doubts around whether the ARCUS platform and I-CreI can deliver solutions that have sufficient value. I intend to continue monitoring the company, however, and hope to update readers in a few months. If nothing has changed for the better by then, then I would expect the stock price to be below current price and no higher than $10, due to the cash burn caused by onerous R&D and G&A costs, lack of profits, intensity of competition, time pressure and absence of milestone payments.

Of course, it will only take one set of good results to cause a sizable uplift in share price, and cement the reputation of ARCUS and I-CreI, but this is a gamble I am unlikely to take personally, since I believe there are better bets in each of the sectors Precision is targeting.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Read the original post:
Precision BioSciences: Incentivised To Deliver, But Outlook Not Promising - Seeking Alpha

CHICAGO, Jan. 20, 2020 /PRNewswire/ -- According to the new market research report "Gene Therapy Marketby Vectors [Non-viral (Oligonucleotides), Viral (Retroviral (Gammaretroviral, Lentiviral), Adeno-associated], Indication (Cancer, Neurological Diseases), Delivery Method (In Vivo, Ex Vivo), Region - Global Forecast to 2024", published by MarketsandMarkets, is projected to reach USD 13.0 billion by 2024 from USD 3.8 billion in 2019, at a CAGR of 27.8% from 2019 to 2024.

MarketsandMarkets_Logo

Download PDF Brochure: https://www.marketsandmarkets.com/pdfdownloadNew.asp?id=122857962

The high incidence of cancer and other target diseases, availability of reimbursement, and the launch of new products are the major factors driving the growth of the market.

The non-viral vectors segment accounted for the largest share of the market, by vector, in 2018

The Gene Therapy Market, by vector, has been segmented into viral and non-viral vectors. Non-viral vectors accounted for the largest share of the market in 2018. This is mainly attributed to the high market penetration of oligonucleotide-based non-viral vector gene therapies.

Browsein-depth TOC on "Gene Therapy Market" 127 - Tables25 - Figures 129 - Pages

The demand for gene therapies for the treatment of cancer is expected to grow at a high rate

Based on indication, the market is segmented into neurological diseases, cancer, hepatological diseases, Duchenne muscular dystrophy, and other indications. The neurological diseases segment accounted for the largest share of the market in 2018. However, the cancer segment is estimated to grow at the highest CAGR during the forecast period owing to the increasing incidence of cancer and the rising demand for CAR T-cell therapies.

Get 10% Customization Research Report: https://www.marketsandmarkets.com/requestCustomizationNew.asp?id=122857962

North America is the largest regional market for gene therapy products

The global Gene Therapy Market is segmented into North America, Europe, the Asia Pacific, and the Rest of the World. In 2018, North America accounted for the largest share of the market, followed by Europe. Moreover, the North American market is estimated to register the highest growth rate during the forecast period. Factors such as the rising prevalence of chronic diseases, high healthcare expenditure, presence of advanced healthcare infrastructure, favorable reimbursement scenario, and the presence of major market players in the region are driving market growth in North America.

The prominent players operating in the Gene Therapy Market include Biogen (US), Sarepta Therapeutics, Inc. (US), Gilead Sciences, Inc. (US), Novartis AG (Switzerland), Amgen, Inc. (US), Spark Therapeutics, Inc. (US), MolMed S.p.A. (Itlay), Orchard Therapeutics plc. (UK), Sibiono GeneTech Co. Ltd. (China), Alnylam Pharmaceuticals, Inc. (US), Human Stem Cells Institute (Russia), AnGes, Inc. (Japan), Dynavax Technologies (US), Jazz Pharmaceuticals, Inc. (Ireland), and Akcea Therapeutics (US).

Browse Adjacent Markets @Biotechnology MarketResearch Reports & Consulting

Get Special Pricing on Bundle Reports:https://www.marketsandmarkets.com/RequestBundleReport.asp?id=122857962

Browse Related Reports:

Regenerative Medicine Marketby Type [Cell-Based Immunotherapy & Cell Therapy (Allogeneic & Autologous Products), Tissue Engineering, Gene Therapy], Applications (Wounds & Dermal, Musculoskeletal, Oncology), Region - Global Forecast to 2024

Story continues

Viral Vector Manufacturing Marketby Type (Retrovirus, Gammaretrovirus, AAV), Disease (Cancer, Infectious Disease, Genetic Disorders), Application (Gene Therapy, Vaccinology), End User (Biotech companies, Research Institutes) - Global Forecast to 2023

About MarketsandMarkets:

MarketsandMarkets provides quantified B2B research on 30,000 high growth niche opportunities/threats which will impact 70% to 80% of worldwide companies' revenues. Currently servicing 7500 customers worldwide including 80% of global Fortune 1000 companies as clients. Almost 75,000 top officers across eight industries worldwide approach MarketsandMarkets for their painpoints around revenues decisions.

Our 850 fulltime analyst and SMEs at MarketsandMarkets are tracking global high growth markets following the "Growth Engagement Model GEM". The GEM aims at proactive collaboration with the clients to identify new opportunities, identify most important customers, write "Attack, avoid and defend" strategies, identify sources of incremental revenues for both the company and its competitors. MarketsandMarkets now coming up with 1,500 MicroQuadrants (Positioning top players across leaders, emerging companies, innovators, strategic players) annually in high growth emerging segments. MarketsandMarkets is determined to benefit more than 10,000 companies this year for their revenue planning and help them take their innovations/disruptions early to the market by providing them research ahead of the curve.

MarketsandMarkets's flagship competitive intelligence and market research platform, "Knowledge Store" connects over 200,000 markets and entire value chains for deeper understanding of the unmet insights along with market sizing and forecasts of niche markets.

Contact:Mr. Shelly SinghMarketsandMarkets INC.630 Dundee RoadSuite 430Northbrook, IL 60062USA : +1-888-600-6441Email: sales@marketsandmarkets.comContent Source: https://www.marketsandmarkets.com/PressReleases/gene-therapy.asp Research Insight:https://www.marketsandmarkets.com/ResearchInsight/gene-therapy-market.asp Visit Our Website:https://www.marketsandmarkets.com

View original content:http://www.prnewswire.com/news-releases/gene-therapy-market-worth-13-0-billion-by-2024---exclusive-report-by-marketsandmarkets-300989478.html

SOURCE MarketsandMarkets

Original post:
Gene Therapy Market Worth $13.0 Billion by 2024 - Exclusive Report by MarketsandMarkets - Yahoo Finance

From our Obsession

New thinking is required to serve an aging population.

Scientists know a lot about the hallmarks of different types of dementia. Alzheimers disease is characterized by buildups of amyloid and tau proteins. Vascular dementia is the result of gnarled and broken blood vessels that normally supply oxygen to the brain. Parkinsons disease and other Lewy Body dementias are caused by misshapen alpha-synuclein proteins in the brain.

Conventional wisdom has it that each of these dementias needs its own treatment. An anti-amyloid drug probably wouldnt work for someone who doesnt have amyloid buildups in their brain.

But to this day, there are no definitive treatmentsor preventive measuresfor any of the dozens of dementias out there. Which has led some researchers to take a more systematic approach: What if there were a single mechanism in the brain that, when faulty, leads to all kinds of dementias? And what if this mechanism, like a switch, could be flipped off?

Thats the thinking of Michael Fossel, the founder of the Michigan-based biotech startup Telocyte, which is developing treatments for Alzheimers. Today (Jan. 14), Fossel published a review articlepostulating that Alzheimers and other dementias are caused by a failing of a workhorse class of brain cells called glia. He also proposes that he and his colleagues at Telocyte, founded in 2015, have a solution: a gene therapy that could target these cells to keep dementia at bay.

The paper is theoreticalits a review, so its not presenting any original data. Its a new way of thinking, and a bold proposition. Its encouraging to see individuals like Dr. Fossel pulling together research and trying to come up with new theories, says Rebecca Edelmayer, the director of scientific engagement at the Alzheimers Association. The Alzheimers Association is a nonprofit and publisher of Alzheimers and Dementia, the journal in which Fossels review article appeared.

But while theories are important, Edelmayer says, they also need to be tested. Gene therapies are still relatively new. And theres reason to wonder about the safety of the gene the therapy would introduce: one that codes for the enzyme telomerase. Before scientists can even begin to test Fossels systematic theory of dementia, theyll need a lot of data demonstrating its safety.

Telomerase has been a focus of longevity research for years. Its an enzyme that lengthens telomeres, which are the genetic caps on the end of our chromosomes. Every time cells divide, telomeres shortenand when telomeres have been sufficiently shaved away, cells enter a state called senescence and stop dividing. Then, they self-destruct.

Shorter telomeres have been correlated with a whole host of age-related health issues: cancer, diabetes, and even forms of dementia. But its not the telomeres themselves that cause these issues, Fossel suggests. As my telomeres shorten, there are a lot of other things going on, too, he says.

The relative length of telomeres, we know, sends a signal to the rest of the cells DNA. As telomeres shorten with cell replication, cells change the way they carry out other genetic instructions, which can result in shoddy protein production. Its a process called the telomere positron effect (paywall), and scientists still dont fully understand it.

Fossel posits that when telomeres shrink in microglial cells, part of the brains immune system, other critical parts of their DNA degrade, tooand that genetic damage can result in many different dementias.

Telocytes gene therapy would aim to rebuild those glial telomeres. That would involve sending an active copy of the telomerase gene, TERT, into the cerebrospinal fluid, carried by a virus. The virus, which should be otherwise benign, isnt great at getting genetic material into specific cells: in mouse models, about 5% of the total therapy winds up in neurons, to no lasting effect, and about 1% winds up in microglial cells, Fossel says. But even with the TERT gene just floating around in the glial cell for a few weeks or months, it might be enough for telomerase to lengthen those end caps and trick the cell into expressing genes like it did in its younger days.

Usually, gene therapies work by introducing new genetic material that replaces a persons faulty or missing genetic code. Telocytes gene therapy, however, wouldnt be replacing a gene: Itd just be giving glial cells another copy of one they already have. All of our cells have the TERT gene embedded in their chromosomes. But the vast majority of cells (save for red blood cells, sperm or egg cells, and cells along parts of the digestive tract) have the gene switched permanently off.

Thats for good reason: Telomerase is active in most forms of cancer. Which is why many scientists fear that inserting a gene that codes for telomeraselike Telocytes gene therapyrisks causing cancer

My main concern is its safety, says Jue Lin, molecular biologist at the University of California San Francisco whose work focuses on studying telomere length and stress levels over time. We dont know whether the over-expression of telomerase will increase the risk of cancer. In the brain, particularly in the glial cells that Fossels proposed gene therapy would target, the cancer in question would likely be glioblastoma, a ravenously growing brain tumor.

Mouse models using telomerase gene therapy in the brain have been promising, with no notable incidence of cancerbut those experiments are imperfect. Mice express telomerase differently than humans do, Lin explains: They have a lot more telomerase, in more tissues than humans. Mice also dont live as long as we do, and cancer takes a long time to develop, Lin says.

And gene therapies carry the risk of a dangerous immune reaction to the virus carrying the therapeutic gene. The viruses used in gene therapy todayand the one Fossel proposes usingshould be safer than the ones used in the early days of gene therapy. Adeno-associated virus, or AAV for short, should elicit only the tiniest of immune responses. But scientists have recently voiced concerns about the long-term safety of gene therapies using AAV.

Given the risks, theres disagreement over whether the telomerase approach is worth pursuing. Its important and interesting to have an additional hypothesis, says Diego Forero, a researcher at the School of Health Sciences at the Fundacin Universitaria del rea Andina in Colombia. His work, which is independent of Fossels, focuses on exposing astrocytes, a type of glial cell in the brain, to telomerase, to see how theyll react. Hes found that telomerase is involved in other cellular functions, like a cells metabolism. In his opinion, its too early to say that Fossels theory should be tested.

Rather than focusing on the potential therapeutic application of telomerase in brain cells, Forero is interested in more basic, exploratory research. He thinks that applying it to a specific targetlike a cure for dementiawouldnt tell scientists enough about all the ways telomerase could affect brain cells.

Those calls for prudence can be frustrating for dementia patients facing a dearth of options. Even with no immediate plans to conduct clinical trials, Fossel says he has already had some 200 people with mild to moderate dementia reach out to him as willing participants. Theyre ineligible for most other clinical trials for dementia therapies, which tend to seek out participants who have risk factors of the disease but minimal symptomsor none at all.

People have faced terrible disease and said Im going to take my chances, says Arthur Caplan, a bioethicist at New York Universitys Langone Medical Center. With vulnerable populations desperate for treatment, peer review from independent scientists becomes even more important. Its critical that the data and research are conducted by parties that dont have a vested financial interest in a certain outcome.

These studies also need to have strong institutional review boards, Caplan says. These boards are required any time researchers are conducting experiments with human subjectsespecially when the risks are so high.

Libella Gene Therapeutics, a Kansas-based biotech startup, is beginning a clinical trial for a telomerase gene therapy to treat broad aging this year. However, its taken its work to Colombia, where the standards for institutional review boards arent as high as they are in the US. Its a tactic informally known as IRB shopping, and it raises eyebrows in the research community.

Were always open to new ideas and novel ways [to treat dementia, Edelmayer says. We have to leave no stone unturned. But, she continued, one of the biggest things we want to see is not just theories. We want to see them tested.

Go here to read the rest:
Could a gene therapy cure dementia? - Quartz

Meet Helen Obando, a shy 16-year-old who likes to dance when her body isnt ravaged by the debilitating symptoms of sickle cell disease. The genetic blood disorder can cause strokes, organ damage and intense pain.

After a lifetime of pain and potential permanent damage to her body, Helen had the opportunity to receive a breakthrough experimental treatment at Boston Childrens Hospital that would make her the youngest person in the U.S. to have her DNA reset in an attempt to cure her sickle cell disease.

The outcome of her gene therapy could help determine how an estimated 100,000 people in the U.S. and millions more around the world are treated. Sickle cell disease most commonly affects people from sub-Saharan Africa, and about 1 in 500 African-Americans have the blood disorder, the most commonly inherited blood disorder in the U.S. But some people with the disease have southern European, Middle Eastern or Asian backgrounds or, like Helen, are Hispanic. For decades, attention and money for research have not matched the scale of the problem.

Why has it taken so long for the scientific research community to push ahead with promising therapies for sickle cell?

Read full, original post: A Teenagers Breakthrough Gene Therapy for Sickle Cell Disease

Visit link:
Teenager's experimental gene therapy treatment could change the lives of millions of sickle cell patients worldwide - Genetic Literacy Project

XconomyBoston

JP Morgans annual healthcare conference convenes in San Francisco this week and Generation Bio CEO Geoff McDonough is betting gene therapy will be among the discussion topics. While such therapies now offer ways to address some rare diseases that previously had no treatment, they also have limitations.

Generation Bio is among the new wave of companies trying to avoid or overcome the challenges facing the current slate of gene therapies. To support its efforts, the Cambridge, MA-based company has raised an additional $110 million for its most advanced programs while also aiming for something more.

It gets us to the clinic, although its almost certain well take the company public ahead of that, McDonough says.

The Series C financing includes crossover investors, firms that back both private and public companies and whose involvement is viewed as a sign a company is preparing to go public. T. Rowe Price led Generation Bios latest round, joined by Farallon, and Wellington Management Company. Also participating in the round were earlier investors Atlas Venture, Fidelity, Invus, Casdin, Deerfield, Foresite Capital, and an entity associated with SVB Leerink. The latest round comes two years after Generation Bio closed a $100 million Series B round.

Currently available gene therapies (and some that are still in development) use an engineered virus to deliver their genetic payloads. But the virus can be a problem. Some people have preexisting antibodies to adeno-associated virus (AAV), the virus used in many gene therapies. And if patients dont already have those antibodies, they can develop them after being dosed with the treatment. That means patients cant receive another dose if they need it, and so far, the durability of gene therapies is not yet known.

Generation Bio avoids viral delivery altogether. The companys gene therapies use closed-ended DNA, or ceDNA, packaged inside a lipid nanoparticle. McDonough says it works just like AAV and it has the added advantage of being easier and less expensive to manufacture compared to AAV-based gene therapies. He adds that if patients need another dose, antibodies wont be a problem. But the company still needs to show that in clinical trials.

Generation Bios most advanced programs are for the blood disorder hemophilia A and phenylketonuria (PKU), an inherited metabolic disorder. There are other companies developing gene therapies for both diseases. Pfizer (NYSE: PFE) has taken over development of SB-525, a hemophilia A gene therapy candidate initially developed by its partner, Sangamo Therapeutics (NASDAQ: SGMO). BioMarin Pharmaceutical (NASDAQ: BMRN) on Monday announced that US and UK regulators cleared the company to begin clinical testing of BMN 307, its experimental gene therapy for PKU. Both experimental treatments use AAV to deliver the therapies to cells.

Besides supporting its hemophilia A and PKU clinical research, McDonough says the new financing will enable his company to look at other rare metabolic disorders such as Wilson and Gaucher disease. He adds that the company will also explore how its technology can be used to deliver therapies to more tissues in the body, such as skeletal tissue and the retina. By being able to reach more tissues, the goal is to expand the scope of gene therapy beyond rare diseases and bring it to the masses, he explains.

McDonough says Generation Bio has been careful not to work with other companies because its technology was still in development. But now that the technology is more mature, the biotech will explore research alliances with larger pharmaceuticalfirms.

I think we will do a partnership this year, he says. The question is in what domain and with which partner.

Photo by Jeremy Bishop on Unsplash

Frank Vinluan is an Xconomy editor based in Research Triangle Park. You can reach him at fvinluan [[at]] xconomy.com.

Read more:
Generation Bio Pockets $110M for Next Wave of Gene Therapy, IPO Plans - Xconomy