Cell therapy has broken new therapeutic ground, but the progress of this drug class in blood cancers has yet to be realized in solid tumors. Big pharmaceutical companies and upstart biotechs are trying various approaches to broaden the scope of these cancer treatments and AstraZeneca is now joining them by buying a startup with technology for developing a new type of personalized cell therapy.

AstraZeneca said Tuesday it has agreed to pay $200 million up front to acquire Neogene Therapeutics, a company that earlier this year received the regulatory green light to begin the first human test of its cell therapy. Another $120 million is tied to the achievement of milestones. The companies expect to close the deal in the first quarter of 2023.

The first cell therapies were made by harvesting a patient’s own T cells and engineering them in a lab to address a target on cancer cells. The cell therapies of Neogene are also highly personalized. The biotech takes a patient’s T cells and engineers them to target neoantigens, novel targets found exclusively on cancer cells due to cancer-associated DNA mutations. Whereas the first generation of cell therapies go after targets on the tumor surface, Neogene, which maintains operations in Amsterdam and Santa Monica, California, claims its T cell receptor-therapies (TCR-Ts) can recognize targets inside a tumor. By addressing previously inaccessible targets, Neogene says its cell therapies can address solid tumors.

A Neogene TCR-T starts with a biopsy of a patient’s tumor. DNA sequencing along with other genomics tools are used to identify the neoantigens of a tumor as well as the genes that code for their receptors. Those genes are introduced into a patient’s T cells, enabling them to recognize a patient’s tumors. But rather than addressing a single target, a Neogene TCR-T will span multiple tumor neoantigens to spark a broader T cell response against the cancer. In a prepared statement, Susan Galbraith, AstraZeneca’s executive vice president of oncology R&D, said Neogene’s capability to discover TCRs complements the cell therapy capability it has built over the last three years.

Neogene’s founders have deep cell therapy experience. The company was founded in 2018 by Ton Schumacher and Carsten Linneman. The duo had previously founded T-Cell Factory, a company that developed technology that discovers tumor-specific T cell receptors. Kite Pharma acquired T-Cell Factory in 2015. Kite’s Yescarta became the second CAR T cell therapy to win FDA approval in 2017, the same year that Gilead Sciences struck an $11.9 billion deal to acquire Kite. Neogene has Kite connections. The startup’s investors include Kite founder and former CEO Arie Belldegrun; David Chang, another former Kite executive, is also a Neogene investor. Neogene disclosed more details about its pedigree and its technology in 2020, when it unveiled a $110 million Series A round of financing. At that time, Linneman told me he estimated clinical testing was two years away.

AstraZeneca’s deal to acquire Neogene comes as the biotech moves its research into clinical testing with its lead program, NT-125. This cell therapy is designed to carry up to five neoantigen-specific TCRs, which together limit the opportunity for a tumor to escape the treatment. Dutch authorities cleared Neogene’s application to begin a Phase 1 test in May. That study, which will be done in partnership with the Netherlands Cancer Institute, is designed to enroll adults with various types of solid tumors.

The broader field of TCR therapies is making progress and growing. Adaptimmune’s work in TCRs has led to alliances with GSK, Astellas, and Roche. In August, startup 3T Biosciences emerged with $40 million and technology licensed from Stanford that screens for TCRs that are specific to cancer cells. South San Francisco-based 3T aims to reach the clinic by 2024.

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Cancer continues to be a big draw for biotech investors, and cancer research is well represented in the past week’s financing activity. Seven biotech companies announced financing rounds to support a range of tumor-targeting therapeutic approaches that include small molecules, oncolytic viruses, and peptide drugs.

Peptides are the focus of FogPharma, which raised the largest financing round of the Thanksgiving holiday-shortened week. The Cambridge, Massachusetts-based biotech is developing a new class of peptide drugs that address therapeutic targets deemed “undruggable.” FogPharma is led by CEO Greg Verdine, a former Harvard professor who has become a biotech entrepreneur. Verdine is also chief executive of LifeMine Therapeutics, a GSK-partnered startup that analyzes fungal genes to discover new drugs.

Arch Venture Partners and Invus are among the financial backers of LifeMine, and those firms also participated in FogPharma’s new $178 million round of funding. The Series D financing comes as the biotech prepares for its first clinical trial. The company says polypeptide drugs from its Helicon platform combine the targeting abilities of antibodies with the features of small molecule drugs: broad tissue distribution, intracellular target engagement, and oral dosing. Lead program FOG-001 is designed to block TCF-blocking beta-catenin to address a dysregulated signaling pathway found in an estimated 20% of all human cancers.

In preclinical research, FogPharma says FOG-001 stopped tumor growth and led to tumor regression. The company plans to submit an investigational new drug application and start Phase 1 testing by mid-2023. The new capital will also support development of FogPharma’s preclinical pipeline, which addresses other biologically validated but elusive cancer drug targets such as TEAD, NRAS, Pan-KRAS, and Cyclin E1.

Here’s a look at the other biotech financings for the past week:

—Nearly three months after Roche reached a deal to acquire cancer drug developer Good Therapeutics in a $250 million deal, a spinout from the biotech called Bonum Therapeutics has raised $93 million in Series A financing. Seattle-based Bonum is developing cytokine cancer therapies for cancer therapies. These drugs will be conditionally activated, meaning that they will activate only when the antibody sensor component of the therapy binds to its target, which is intended to reduce toxicity.

The technology that is the basis for Bonum’s drugs was validated by Good. Good’s financial backers, including Rivervest Venture Partners, Roche Venture Fund, Digitalis Ventures, 3×5 Partners, and Codon Capital, teamed up again for Bonum’s Series A financing, which added a new investor, Vivo Capital.

—Clinical-stage CG Oncology closed a $120 million Series E financing. The Irvine, California-based biotech’s lead drug candidate, CG0070, is an oncolytic virus that has reached Phase 3 testing as a monotherapy for non-muscle invasive bladder cancer that does not respond to Bacillus Calmette-Guerin, the most common intravesical immunotherapy used for treating early-stage bladder cancer. A Phase 2 study is also underway testing CG0070 in combination with Merck immunotherapy Keytruda. CG Oncology said it will use the new capital to advance its lead programs toward FDA review and broaden its drug pipeline to address other unmet needs in urologic cancer.

—CatalYM closed a €50 million Series C financing to expand Phase 2 clinical testing of its lead program, which is in development for treating solid tumors. The antibody drug candidate, visugromab, is engineered to neutralize Growth Differentiation Factor-15 (GDF-15), a tumor-produced protein that regulates immune cell activation and stops immune cells from infiltrating tumor tissue. Visugromab’s solid tumor test is evaluating the drug in combination with a type of immunotherapy that blocks the checkpoint protein PD-1. Preliminary data are expected in early 2023. Munich, Germany-based CatalYM’s new round of financing was co-led by Brandon Capital and Jeito Capital.

—Casma Therapeutics closed $46 million in Series C financing to bring its lead program for MYD88 mutant lymphoma through the preclinical research that will support an investigational new drug application. The Cambridge, Massachusetts-based company develops therapies that leverage autophagy, a mechanism for recycling old or damaged cellular components. A similar approach called targeted protein degradation focuses only on proteins and peptides. But autophagy can address larger cellular components such as organelles.

—Rezo Therapeutics, a University of California at San Francisco spinout that is developing new cancer drugs, launched with $78 million. The technology of the San Francisco-based company identifies how mutations rewire cancer-driving networks, using that insight to uncover tumor-specific drug targets. This tech platform comes from UCSF’s Quantitative Biosciences Institute. Rezo’s Series A financing was led by SR One, a16z Bio + Health, and Norwest Venture Partners.

—Opna Bio, a startup developing cancer therapies acquired from Plexxikon, unveiled $38 million in Series A financing. The company’s co-founders include Douglas Hanahan, a distinguished scholar in the Lausanne Branch of the Ludwig Institute for Cancer Research and emeritus professor at the Swiss Federal Institute of Technology Lausanne. Opna’s launch and financing comes as research from Hanahan’s EPFL laboratory was published in the journal Science describing the role of fragile X mental retardation protein (FMPL) as an immuno-oncology target. Opna has licensed this FMPL technology. Longitude Capital and Northpond Ventures led the Series A round of Opna, which maintains operations in Lausanne, Switzerland, and South San Francisco.

—In non-cancer biotech funding news, MBX Biosciences raised $115 million to develop therapies in a new class of peptide drugs, including a lead program in early-stage clinical development for hypoparathyroidism. Carmel, Indiana-based MBX says its precision endocrine peptides, or PEPS, overcome limitations of traditional peptide drugs. In addition to supporting lead PEP product candidate MBX 2109, MBX said the new capital will support its preclinical drug pipeline. The Series B round of funding was led by Wellington Management.

—Bain Capital Life Sciences led a $107 million investment in Jnana Therapeutics as the biotech continues Phase 1 testing that could demonstrate clinical proof of concept for its lead program, a potential treatment for phenylketonuria. The inherited metabolic disorder leads to a deficiency of phenylalanine hydroxylase, an enzyme required to break down an amino acid called phenylalanine. Jnana’s drug, JNT-517, is small molecule designed to block phenylalanine reabsorption in the kidney, which in turn reduces blood levels of phenylalanine.

Separate from Jnana’s Series C financing, the biotech announced a second collaboration with Roche focused on the discovery of small molecule drugs for cancer, immune-mediated diseases, and neurological disorders. The Swiss pharmaceutical giant is paying Jnana $50 million up front; milestone payments could reach up to $2 billion.

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When Biogen’s experimental treatment for amyotrophic lateral sclerosis (ALS) missed the main goal of a pivotal study last year, the drugmaker said further analysis could yield better results. Additional data now show that treatment over a longer period of time led to improvement on several measures of the neuromuscular disorder.

The latest clinical trial results were published Wednesday in the New England Journal of Medicine. The data lend additional support for the drug, tofersen, which has been submitted for FDA review and is expected to receive a regulatory decision in early 2023.

Tofersen is an antisense oligonucleotide, a type of drug comprised of small pieces of DNA or RNA. The Biogen drug addresses a subset of ALS patients whose disease is driven by mutations to the SOD1 gene. These mutations lead to abnormal versions of the SOD1 protein believed to contribute to motor neuron dysfunction and cell death. Tofersen is designed to bind to and degrade SOD1 messenger RNA, which in turn reduces synthesis of SOD1 protein.

The main goal of the randomized, placebo-controlled Phase 3 test of the drug was to evaluate ALS patients on various functional measures at 28 weeks. According to results reported last October, the observed patient improvement was not enough to show statistical significance. However, investigators at the time noted that the results showed reductions in SOD1 protein and neurofilaments, filaments found in neurons that are considered a potential biological indicator of neurodegenerative disease.

Biogen did not give up on the drug. In June, the company presented data analysis  in which the randomized study at 28 weeks was combined with an open-label extension study at 52 weeks. In that new 52-week analysis, Biogen reported slower declines in measures such as respiratory function and muscle strength in those who started on tofersen earlier—the patients who received the study drug at the start of the study compared with those who started on placebo and were switched over to tofersen at week 28 to begin the extension study. These are the results that are now published in the New England Journal of Medicine.

Timothy Miller, co-director at the ALC Center at the Washington University School of Medicine and the principal investigator of the tofersen clinical trial, said in a prepared statement that in addition to the lowering of SOD1 protein, the drug led to “substantial lowering of neurofilament levels, which I interpret as potentially slowing the underlying disease process.” Miller added that looking at the results in the later time points in the open-label extension study show “meaningful clinical benefit.” The New England Journal of Medicine article notes that comparisons of earlier initiation of tofersen versus delayed initiation are still being evaluated in the extension stage of the clinical trial.

The 52-week data were part of Biogen’s submission seeking FDA approval. The FDA accepted that application in July, setting a Jan. 25, 2023 target date for a regulatory decision. At the time, the agency said it planned to convene an advisory committee meeting to discuss the application. The date for that meeting has not yet been set.

The published data for Biogen’s ALS drug come as an ALS drug from Amylyx Pharmaceuticals is making its way through regulatory review. Two weeks ago, an FDA advisory panel voted 7-2 in support of recommending approval of that company’s experimental ALS treatment, AMX0035. An FDA decision for the Amylyx drug is due by Sept. 29.

Meanwhile, another ALS drug developer, BrainStorm Cell Therapeutics, is taking a shot at FDA approval. Last year, the FDA called out Brainstorm’s analysis of its ALS drug, Nurown, saying that that in addition to missing the main clinical trial goal, the results fell did not show patient benefit. Nevertheless, Brainstorm said last month that it plans to seek FDA approval of its ALS therapy.

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Third Harmonic Bio is joining the public markets with a $183.3 million IPO that’s a stark outlier in the context of the near absence of new stock offerings in 2022. Record inflation, rising interest rates, and recessionary fears have chilled public financing activity in the year to date.

Not only has Third Harmonic pulled off a stock sale, but it was also able to boost the deal size. Wednesday evening, the biotech offered 10.9 million shares priced at $17 each, which was the midpoint of its targeted price range. When the company set financial terms for the IPO last week, it aimed to sell 9 million shares. Third Harmonic shares are slated to begin trading Thursday on the Nasdaq under the stock symbol “THRD.”

Cambridge, Massachusetts-based Third Harmonic is an inflammation and allergy biotech whose main asset, licensed from Novartis, has potential applications in several conditions. The small molecule, THB001, is designed to block KIT, a receptor that regulates mast cells, a type of immune cell. Mast cells play a role in many inflammatory conditions and blocking it has shown efficacy in some disorders, such as asthma. With the ability to selectively block KIT compared to other small molecule drugs, THB001 could avoid off target effects, the company said in its IPO filing.

So far, Third Harmonic has generated encouraging early Phase 1 data for its small molecule. Its lead disease target is chronic urticaria, an inflammatory skin disorder that leads to hives. Third Harmonic’s effort to block KIT trails a drug from Celldex Therapeutics. The Celldex drug, barzolvolimab, is in early clinical development for urticaria and other inflammatory disorders. But as an antibody, the Celldex drug is given as an intravenous infusion. The formulation of Third Harmonic’s drug as a more convenient oral pill should give it a dosing edge.

With the IPO cash, Third Harmonic plans to press ahead with multiple clinical trials testing its drug candidate. Between $80 and $90 million is earmarked for continuing clinical development of THB001 in urticaria by completing a Phase 1b study and starting a Phase 2 study, according to the IPO filing. The company expects to report initial data from the Phase 1b study in the first half of 2023. Applications to begin the Phase 2 tests in the U.S. and Europe are expected in the first half of 2024.

Another $30 million to $40 million of the IPO cash is planned for clinical development of the drug in other indications, including the completion of a Phase 1b test in asthma. Preliminary data from the asthma study are expected in the second half of 2024, according to the filing.

As of the end of the second quarter of this year, Third Harmonic reported having $112.7 million in cash and cash equivalents. The biotech projects that its cash reserves plus the funds from the IPO will support operations through 2025.

Here’s a look at some other stock market news this week for biotech companies:

No IPO for Elicio

Cancer immunotherapy developer Elicio Therapeutics is withdrawing its planned IPO. The Boston-based biotech had initially filed to go public in 2021, when financial conditions were more friendly for stock offerings. In a Sept. 13 letter to the Securities and Exchange Commission, Elicio offered no reason for the withdrawal other than to say it does not plan to pursue the stock offering at this time.

Elicio left the door open for a future IPO, asking the commission to credit the fees paid so far toward future use. The company’s lead drug candidate, ELI-002, is in Phase 1/2 testing as a potential treatment for cancers characterized by the KRAS mutation.

Know Labs’ stock finds a new home

Shares of medical diagnostics technology company Know Labs, which previously traded over the counter, have been uplisted to the NYSE American Exchange. Those shares are set to begin trading on Friday under a new stock symbol: “KNW.”

Seattle-based Know Labs says its technology directs electromagnetic energy through a substance or material to capture a unique molecular signature. The company is using this “Bio-RFID” technology to develop a non-invasive glucose monitor that provides users real-time information about their blood glucose.

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The IPO window has been closed to most biotech companies this year, but Third Harmonic Bio is pushing it open with a drug from Novartis that might work better than the wide selection of inflammation medicines already available to patients. The biotech has early clinical data showing signs of efficacy. Now the company wants to tap the public markets to finance further clinical development of the molecule in multiple inflammatory disorders.

Cambridge, Massachusetts-based Third Harmonic did not set any financial terms for the stock sale outlined in the preliminary IPO paperwork filed with regulators on Tuesday. However, IPO research firm Renaissance Capital said the offering could reach up to $150 million. Third Harmonic has applied for a Nasdaq listing under the stock symbol “THRD.”

Third Harmonic’s research focuses on the mast cell, a type of immune cell in the blood whose dysfunction is associated with the development of many allergic and inflammatory diseases. These cells are found throughout the body and are prominent on tissue with exposure to the external environment, such as the skin, respiratory tract, and gastrointestinal tract.

Lead Third Harmonic drug THB001 is a small molecule designed to block KIT, a cell surface receptor whose role is to regulate mast cells. In the IPO filing, the company notes that KIT inhibition has shown signs of efficacy in mast cell-mediated diseases such as asthma. A wide range of therapies already treat asthma and other inflammatory disorders, but Third Harmonic notes in the filing that many of these drugs are insufficient because they target the compounds that are produced by mast cells, such as histamines. For many diseases, multiple compounds are involved.

“As a result, we believe that targeting mast cells directly through highly selective inhibition of KIT is key to achieving the clinical efficacy needed for broad symptomatic relief across a range of allergic and other inflammatory disorders,” Third Harmonic said in the filing.

So far, Third Harmonic has tested its lead drug in a Phase 1a clinical trial. Though this study only enrolled healthy volunteers, the drug flashed indications of efficacy. The company reported that blood tests showed dose-dependent declines in tryptase, an enzyme released when mast cells are activated. Third Harmonic now aims to test whether its drug can treat chronic urticaria, an inflammatory skin condition characterized by hives and an itchy rash. The company said in the filing that it has submitted a clinical trial application in Europe for a dose-escalation Phase 1b study intended to show proof-of-concept in this disease. Data are expected in the second half of next year.

Asthma is the next disease target. Third Harmonic plans to start a Phase 1b study in the first half of 2023 and report data in the second half of 2024. The biotech is also eying the start of Phase 2 tests in chronic spontaneous urticaria. Those studies in the U.S. and Europe are planned for the first half of 2024. Third Harmonic describes its lead asset as a “pipeline in a product.” The company is exploring other diseases where stopping mast cell-driven inflammation may offer relief.

Third Harmonic has competition in its pursuit of a better drug for urticaria, a condition whose first line of treatment is antihistamines. Blocking KIT is the objective of Celldex Therapeutics drug barzolvolimab, formerly known as CDX-0159. The Hampton, New Jersey-based biotech has reached early clinical development in urticaria and other inflammatory disorders. But as an antibody, that drug must be given as an intravenous infusion. Third Harmonic hopes that the oral formulation of its KIT-blocking drug gives it an edge.

Third Harmonic is led by CEO Natalie Holles, who previously served as chief executive of gene therapy developer Audentes Therapeutics (now a part of Astellas Pharma). Venture capital firm Atlas Venture founded Third Harmonic in 2019. That year, it licensed THB001 from Novartis for $400,000 cash and an equity stake in the emerging biotech. Much more could be paid out depending on the progress of the research: $31.7 million is tied to in development milestones and up to $200 million in sales and commercialization milestones. Novartis would also earn royalties from the sale of any approved products.

Third Harmonic raised $155 million in its start, most recently a $105 million Series B round that was announced in February. Atlas is the largest shareholder with a 37.9% stake, according to the filing. The Novartis Institutes for BioMedical Research owns 9.4% of the company.

As of June 30, Third Harmonic’s cash position was $112.7 million, which the company said will be enough to fund operations for at least 12 months. Third Harmonic plans to use the IPO cash to continue clinical development of TBH100, specifically the Phase 1b study in chronic inducible urticaria and the Phase 2 test in chronic spontaneous urticaria. The cash will support the planned Phase 1b test in asthma. The biotech also states in the filing that the capital may be deployed toward the development or acquisition of other programs.

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Ahead of a planned booster vaccination campaign this fall, the U.S. government has locked up supply of Moderna Covid-19 vaccines designed to protect against both the original strain of the virus as well as the omicron subvariants that are now circulating widely.

According to terms announced Friday, Moderna will supply the government with 66 million doses of its booster vaccine candidate. The contract includes the option to purchase up to 234 million booster doses. Moderna could be paid up to $1.74 billion, depending on how many doses are ordered.

The Moderna vaccine, named Spikevax, received FDA approval in January for those 18 and older. That vaccine was designed to address the original strain of the novel coronavirus. The company has also been developing two different booster candidates, each a bivalent vaccine that protects against two different strains. Both of these new vaccines will protect against the original strain. One of them, mRNA-1273.222, will also contain the BA.4/5 omicron strain that is dominant in the U.S., consistent with booster guidelines that the FDA set last month. The second booster candidate, mRNA-1273.214, addresses the BA.1 subvariant, which may be more applicable to other regions in the world.

The contracted supply of Moderna boosters is in addition to the agreement the government struck for 105 million bivalent booster doses of the Pfizer/BioNTech Covid-19 vaccine, plus the option to purchase up to 195 million additional doses. Both boosters will need FDA authorization and a recommendation from the Centers for Disease Control and Prevention. If these new shots pass muster with both agencies, they could be ready to go into arms in early fall, the Department of Health and Human Services said. Citing unnamed sources, The New York Times reported that the Biden administration plans to offer the updated Covid-19 shots in September.

As of now, boosters have FDA authorization for those 50 and older as well as those 12 and older who have conditions that impair their immune systems. The Times reported that due to the rising number of Covid-19 cases, some federal health officials advocated for broadening booster eligibility of the current vaccine ahead of the rollout of the retooled versions. But after the companies assured government officials that they could deliver their bivalent boosters by mid-September, the FDA and CDC decided it would be better to focus on the fall vaccination campaign with the new versions of the shots, the Times reported.

According to the CDC, 603.7 million vaccine doses have been administered in the U.S. The agency calculates that 78.8% of the U.S. population has received at least one dose and 67.2% of the population is fully vaccinated (defined as those who have received the second dose of a two-shot vaccine or one dose of the single-shot Johnson & Johnson vaccine). Of those who are fully vaccinated, the CDC reports that 107.9 million people have received a booster shot. More than half of the total booster-eligible population has yet to receive a booster shot, the CDC’s latest data show.

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heart, doctor, cardiac

Novartis’s main offerings for cardiovascular disease are drugs prescribed as a response to symptoms. However, heart problems can develop years before signs appear and the pharmaceutical giant wants to find new approaches to these disorders. A new partnership aims to develop artificial intelligence-based software that detects hidden cardiovascular conditions.

The collaboration is with Anumana, which develops algorithms that are applied to electrocardiograms (ECG). The agreement calls for Cambridge, Massachusetts-based Anumana to develop algorithms that could be applied to patients with previously undetected life-threatening heart disease. These algorithms are intended to help identify problems so physicians can intervene sooner.

“Cardiovascular disease is a widespread and multifactorial disease and, in order to mitigate its impact, we must look beyond therapeutic innovation and reimagine how we approach cardiovascular care,” Victor Bulto, president of Novartis Innovative Medicines U.S., said in a prepared statement. “Novartis is proud to collaborate with Anumana on innovative and data-driven solutions to better predict the risk of life-threatening heart disease, further driving forward our commitment to improving patient experiences and population health outcomes in this patient population.”

No financial terms of the multi-year collaboration were disclosed.

Anumana was formed by the Mayo Clinic and Nference, a company that uses unstructured electronic medical records data from medical centers to develop new diagnostics and treatments. The Anumana joint venture builds on an existing partnership between the Mayo Clinic and Nference. They launched the startup last year and backed it with a $25.7 million Series A investment. Anumana says it has since closed a $60 million Series B round of funding.

The Novartis collaboration could make the ECG, a widely used and inexpensive test, a wealth of information for cardiovascular analysis. Anumana said the alliance builds on its own efforts to develop AI-enabled software that detects signals from ECGs that humans cannot interpret. The new partnership is focused on developing software that can detect previously undiagnosed left ventricular dysfunction, which is also referred to as a weak heart pump. This condition can lead to heart failure.

In addition, Anumana said that the AI will screen for atherosclerotic cardiovascular disease, which can lead to heart attack and stroke. The research includes development of a digital point-of-care solution that can guide the use of drugs. The goal is to reduce the risks of hospitalizations and cardiovascular death. Under the Novartis partnership, Anumana will work with experts at the Mayo Clinic.

“This collaboration has the potential to transform the use of a ubiquitous inexpensive test, the ECG, with the aim of democratizing disease detection and helping medical care teams to proactively manage heart disease ahead of time and prevent some clinical events from ever happening,” Dr. Paul Friedman, chair of the department of cardiovascular medicine at Mayo Clinic and chair of Anumana’s Mayo Clinic board of advisors, said in a prepared statement.

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Voyager Therapeutics is losing Neurocrine Biosciences as a research partner on an experimental Parkinson’s disease treatment, the latest in a string of setbacks for the biotech’s efforts to develop gene therapies addressing neurological disorders.

Cambridge, Massachusetts-based Voyager disclosed late Tuesday that Neurocrine provided a termination notice on the Parkinson’s candidate NBlb-1817, which is currently in mid-stage clinical testing. The decision follows the FDA’s December decision to place a clinical hold on that program due to safety concerns.

Termination of the partnership on the Parkinson’s gene therapy will be effective Aug. 2. The collaboration agreement requires Neurocrine to provide 180 days written notice of a termination. The San Diego biotech acknowledged providing that notice in its own regulatory filing. Three other programs covered by the agreement, one for Friedreich’s ataxia and two others in the discovery stage, are not affected by Tuesday’s decision and will continue, Voyager said.

The alliance began in 2019 when San Diego-based Neurocrine pledged $165 million in cash and stock to Voyager. Of the four programs covered by the pact, the Parkinson’s candidate was the most advanced. According to the deal terms, Neurocrine was responsible for funding Phase 2 clinical development. After the study produced data, Voyager held the option to split the rights to the gene therapy with Neurocrine, sharing in further development costs. Alternatively, Voyager could grant its partner full global rights in exchange for milestone payments pegged to sales.

Prior to the Covid-19 pandemic, Neurocrine anticipated advancing the Parkinson’s gene therapy to a pivotal study in the second half of 2020, the company said in its annual report. The pandemic and the clinical hold stalled that timeline.

Voyager uses engineered viruses to deliver gene therapies to the brain. Parkinson’s is characterized by a lack of dopamine, a brain chemical that’s key to controlling muscle movement. Standard treatment includes prescriptions of levodopa, which is converted by a brain enzyme into dopamine.

As Parkinson’s progresses, a patient has less of that key enzyme in parts of the brain where it is needed to convert levodopa to dopamine, Voyager states in its filings. The Parkinson’s candidate is designed to deliver a gene directly into the neurons where dopamine receptors are located, providing the instructions the brain needs to make the key enzyme.

The Parkinson’s gene therapy is administered via a direct injection into the brain. For its amyotrophic lateral sclerosis and Friedreich’s ataxia programs, the company is exploring other approaches, including spinal or intravenous injections.

In its announcement of the end of the partnership in Parkinson’s, Voyager said Neurocine based its decision on a review of its portfolio and the prioritization of other programs in its pipeline. No mention was made about the safety of the Parkinson’s gene therapy. When Voyager disclosed the clinical hold in December, it said that a Neurocrine safety report noted MRI abnormalities in some study participants. It also said the independent board responsible for monitoring the safety of study participants requested a pause on dosing of patients until it could review additional data.

Until the alliance on NBIb-1817 is officially terminated in August, Neurocrine is the company of record for the clinical program. Voyager said that last month, the FDA informed Neurocrine of the information needed to respond to the clinical hold. In addition to an assessment of how the therapy may have contributed to the adverse findings, Voyager said the agency wants a mitigation plan to manage them along with supportive data to justify that the benefit of the therapy outweighs its risks.

Voyager said it will support Neurocrine on any imaging or clinical assessments requested by data safety monitors of the study, as well as any information sought by the FDA. The company added that it is evaluating the financial effect the termination will have on the company and the future of the Parkinson’s program.

The end of the partnership on the Parkinson’s gene therapy marks the second time a company has passed up the opportunity to advance that program. Sanofi was Voyager’s first partner on the experimental therapy, committing $100 million up front in 2015 for rights to several gene therapies for brain disorders. At the time of the deal, the Parkinson’s gene therapy was in early-stage testing. In 2017, Sanofi returned the therapy to Voyager after the biotech declined to amend the original deal to grant the pharma giant a share of the U.S. rights to the program.

The loss of Neurocrine as a partner in Parkinson’s comes a little more than six months after an alliance with AbbVie ended. That partnership focused on developing gene therapies for Alzheimer’s and Parkinson’s. AbbVie terminated the alliance before either program reached Phase 1 testing, at which point Voyager would have become eligible for additional payments from the North Chicago, Illinois-based pharma company.

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