Johnson & Johnson drug nipocalimab is in late-stage clinical testing in a rare neuromuscular disorder, and if it stays on track could become the third-to-market drug in its class for that indication. But the pharmaceutical giant now has encouraging preliminary data from a separate test in a rare blood disorder affecting fetuses, helping to build the therapy’s case in a life-threatening disease with no approved therapies.

The data announced Monday are from a Phase 2 clinical trial in severe hemolytic disease of the fetus and newborn (HDFN). Stemming from the incompatibility of the infant’s blood type and the mother’s blood type, this disease leads to the mother’s blood crossing the placenta and attacking fetal red blood cells. The resulting anemia can become fatal to the fetus.

Nipocalimab is intended to reduce levels of antibodies implicated in several antibody-driven diseases. The drug is itself an antibody designed to selectively bind to the Fc receptor (FcRN) of immunoglobulin G (IgG), the most common antibody circulating in the blood. J&J’s Janssen Pharmaceutical Companies division said Monday that Phase 2 results showed most of the pregnant patients who received the experimental drug and achieved a live birth did not need an intrauterine transfusion throughout the entire pregnancy, which was the main goal of the study. The number of patients achieving this goal was not specified.

Katie Abouzahr, vice president, autoantibody portfolio development leader at Janssen Research & Development, said in a prepared statement that the full Phase 2 results will be presented at an upcoming scientific medical meeting. She added that the company plans to advance the drug to a pivotal Phase 3 study in this indication.

Nipocalimab joined the J&J pipeline in 2020 via the pharma giant’s $6.5 billion acquisition of Momenta Pharmaceuticals, a biotech that developed drugs by analyzing the interaction of antibodies and receptors that modulate immune responses. Nipocalimab was Momenta’s lead asset, having reached pivotal testing in warm autoimmune hemolytic anemia (WAIHA), a rare disorder in which antibodies destroy healthy red blood cells.

Momenta had envisioned nipocalimab as applicable to multiple autoimmune conditions. J&J embraced that potential and is currently testing the drug in nine clinical trials—six in immunology and three in neuroscience. Those studies span diseases characterized by alloantibodies, which are produced following exposure to a foreign antigen, such as the maternal antibodies that lead to HDFN; diseases characterized by autoantibodies produced in response to the body’s own tissues; and rheumatological disorders such as rheumatoid arthritis and lupus.

Under J&J, nipocalimab has reached pivotal testing in myasthenia gravis, in which autoantibodies interfere with the communication between nerves and muscles. In 2021, FDA-approval of Argenx’s Vyvgart in myasthenia gravis made it the first FcRn-targeting drug to pass the agency’s regulatory bar. The biotech is also developing the drug for other rare antibody-driven disorders. UCB is on Vyvgart’s heels with rozanolixizumab, an FcRn-blocking drug that was submitted for FDA review last month.

The pivotal study of nipocalimab in myasthenia gravis is expected to produce data in 2024, J&J Chairman and CEO Joaquin Duato said during the company’s presentation last month at the J.P. Morgan Healthcare Conference. The most advanced immunology clinical test of the FcRn-targeting drug is the pivotal test in WAIHA. That clinical trial may have a data readout this year, Duato said. A Phase 2 test in rheumatoid arthritis is also expected to yield data this year, he added.

Photo: Niels Wenstedt/BSR Agency, via Getty Images

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Life science organizations faced down an array of daunting challenges during the last three years: a global health crisis, supply chain upheaval, and uncertain economic climate, just to name a few. But if we can say the dust is beginning to settle, we can also look to the future with the knowledge that uncertainty will persist – and that we should be prepared. How can companies prepare for an unpredictable year ahead?

Many pharma and medical device companies will look inward, with the goal of standardizing and modernizing even highly regulated activities. They’ll lean into new approaches for specific challenges, and apply purpose-built technology across drug and device development. Here’s a closer look at some important industry trends for 2023.

Tech maturation matters

Pharmaceutical companies continue to forge ahead in their quest to create a truly end-to-end insights management function. Teams understand that insight generation and analysis are vital to the success of new drug development – but may lack the willingness to devote significant business resources to solving the problem.

Happily, even in a notoriously conservative and risk-averse industry, leaders are coming around to the idea that they can solve the problem with technology. Next year, pharma companies will begin putting both minds and money behind the push to put insights management into the spotlight as a strategic business pillar.

One way they’ll do this is by using artificial intelligence to support – not replace – talented humans who don’t have enough time to manually comb through reams of patient data, medical records, and other important sources of information. For pharmaceutical teams, 2023 will be the year of understanding that AI can be a benevolent partner rather than an intimidating threat.

What’s the danger of ignoring AI? Teams that don’t understand AI applications run the risk of missing out on key insights, and all the opportunities those can provide. This can have a particularly meaningful impact on applications like precision medicine, where developing the best treatment pathway often requires analyzing information about different aspects of the patient experience.

While much of this information is obtained from structured data from electronic medical records, there is also valuable information contained in the unstructured text of physician notes, referral forms, and medical charts. Developing precision therapies also requires input from global experts who won’t necessarily turn up in the usual publishing and speaking circuits. This is an ideal case for technologies that are specific to life science, where gaps in knowledge can interfere with the expedient development of precision and targeted therapies.

Adding agility where it counts

Like other industries, pharmaceutical and medical device companies are eager to return to the days of in-person meetings and busy show floors. But as folks return to racking up frequent flyer miles, an old problem is rearing its head: at in-person events, where do the insights go?

How are important observations collected and shared, and how will that information make its way into the mix with data from other channels, like virtual meetings and social platforms? As organizations balance traditional and tech-enabled ways of working, technology will stay in the picture to add process and consistency.

What does this look like in practice? Teams will gladly return to the muscle memory of an in-person medical congress, but it will be far less chaotic: they’ll use social listening to understand trending topics ahead of and during the event, adding currency to their real-time conversations. They might share same-day observations in a virtual venue and achieve alignment on important discussions before they pack to go home. And once the event is over, the conversations can continue online, with sentiment analysis tools to potentially shorten the time from insight to action by weeks, or even months.

Increasing the all-important agility factor simply equips life science organizations to have more choice in engaging truly global audiences, eliminating traditional roadblocks like travel time and expense, disparate geographical locations, and different preferred languages. Having experienced first-hand what it’s like to work in a world where travel – even as far as an in-town office or clinic – is impossible, the importance of this flexibility can’t be overstated.

As pandemic-induced limitations fell away, many old habits returned. Some, like traveling and meeting in person, were welcomed. Others, such as congress chaos and deluges of data, have been less well-received. The year ahead will be about figuring out how to move forward with flexibility and preparedness when – not if – the next challenge arises.

Photo: Feodora Chiosea, Getty Images

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Congress passed the FDA Modernization Act 2.0 last week removing the requirement to use animal testing in drug development. This will allow drug companies the option to use alternative safety-testing models when making new drug submissions.

This is important because the Federal Food, Drug and Cosmetics Act of 1938, which is still in force, mandates animal testing for every new drug development protocol. Advocates of non-animal experimentation have argued that the cost of animal research is high—in dollars, in time, and in delays in approvals of beneficial drugs for human use. They also maintain that some drugs that were deemed safe by animal studies went on to cause harm in human subjects in clinical testing, although this last position is poorly quantified.

Once the FDA Modernization Act 2.0 is enacted, a transitional moment will follow. The section of the House bill that allows for alternatives to animal use to be incorporated into pre-clinical testing outlines approaches most likely to predict human response based on scientific evidence. These include cell-based assays; organ chips and microphysiological systems; and sophisticated computer modeling. Several of these approaches allow drug developers to incorporate safety assessment alternatives that are robust enough to convince regulators that a program has been adequately de-risked.

The bill comes at a pivotal time; modern toxicity testing has been moving away from a reliance on animal studies. One substitute has been mechanism-based testing strategies, such as cell-based assays. These are already being used as research tools to support the interpretation of in vitro toxicity data, as well as the design of in vitro experiments, and considerable progress has been achieved in making assays available and deployable in a user-friendly form.

So-called organ chips and microphysiological systems began to be used more frequently during Covid-19 drug and vaccine testing, which reportedly helped researchers to better understand how Covid-19 interacted with human organs and elicited an immune response. Using human cells and engineered structures, these approaches create an environment that mimics or models the function of organs, and they may have application in testing drug efficacy in genetically diverse human populations using human genetic material.

The average cost of bringing a drug to market is about $2 billion, of which more than half is spent on clinical trials. But before trials are conducted, researchers are increasingly employing computer modeling, a technology that has been expanding for several decades and which provides several benefits.

Sophisticated modeling that uses in-silico, computer-based testing with virtual patients, biosimulation is fast and relatively inexpensive and reveals rich information about how a drug would perform and how to best design a trial before the drug is ever tested in patients. Biosimulation also offers the flexibility of computer-based testing, allowing developers to optimize trial design and dosing for different patient populations.

By easing regulatory requirements for animal testing, the Act allows scientists to use innovative, leading-edge technologies more fully in future drug development strategies.  These alternatives are not yet the complete answer, but by increasingly taking a “totality of evidence” approach where the combination of multiple data points can be used to assess whether a confidence threshold is reached in relation to the safety of a drug at a particular dose, regulators are allowing developers to accelerate the process.

Now that Congress has passed the FDA Modernization Act, drug companies should consider how to take advantage of the translational tools outlined above, which can be an important part of the drug developer’s arsenal. Depending on how they are used, they can result in researchers more cost-effectively developing the lifesaving drugs and vaccines that patients need, faster.

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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.

Photo: Christopher Furlong, Getty Images

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A CinCor Pharma drug intended to offer a novel alternative to currently available hypertension treatments has failed a Phase 2 study. Nevertheless, CinCor points to better results in a pre-specified subgroup of patients representative of many hypertension patients. While the biotech firm contends the data will guide the design of a study that could support regulatory approval, these preliminary results could also limit the drug’s scope by tens of millions of patients.

Investors took the dimmer view of prospects for the CinCor drug, baxdrostat, and the Waltham, Massachusetts-based biotech’s shares sank Monday more than 47% from Friday’s closing price.

The preliminary results reported Monday are from a dose-finding Phase 2 study enrolling 249 patients who were randomly assigned to receive one of three doses of the experimental CinCor drug or a placebo once a day for eight weeks. Those patients have uncontrolled hypertension, defined as needing up to two blood pressure medications at the maximally tolerated doses. While reductions in blood pressure were observed at all three doses of the CinCor drug, the changes were not enough to meet the main goal of showing a statistically significant reduction in seated systolic blood pressure after eight weeks.

However, a statistically significant reduction was reported in 116 non-Hispanic patients (47% of patients in the trial), a group that includes Black patients who CinCor notes represent about 81% to 89% of people with hypertension in the U.S. In the pre-specified subgroup, CinCor reported that the highest of the three doses tested showed a placebo-adjusted reduction of 12.6 millimeters of mercury, the measure of blood pressure.

“It seems there is a sizable population that could, potentially if confirmed within a Phase 3, could benefit with double-digit reduction in this uncontrollable population,” CEO Marc de Garidel said, speaking during a conference call on Monday.

Hypertension is currently treated with drugs that lower blood levels of aldosterone, a blood pressure-regulating hormone. But extended use of these medicines–angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)–can lead to aldosterone breakthrough, in which blood levels of the hormone return and even exceed prior levels.

CinCor’s baxdrostat works differently than ACE inhibitors and ARBs. The small molecule is designed to block an enzyme that is key to aldosterone synthesis in the adrenal gland. This approach is intended to stop production of the hormone. CinCor Chief Medical Officer Mason Freeman attributed the Phase 2 failure to a high placebo response driven by lack of adherence to a drug regimen that included continuing the anti-hypertensive drugs patients had already been prescribed. Inconsistencies in taking these drugs could have affected the results, he said. Freeman pointed to five sites in particular that were notable for lack of adherence to the drug regimen. CinCor plans to measure background medication use as part of its analysis of the failed study.

Despite missing the trial’s main goal, Freeman said the study met two key company goals: identifying the patient population that had a robust response and confirming that the high dose is the most efficacious one to evaluate in a Phase 3 clinical trial.

The preliminary data reported Monday come nearly four months after a separate Phase 2 study posted data in treatment-resistant hypertension, defined as patients taking at least three blood pressure medications at the maximally tolerated doses, one of which is a diuretic. CinCor said in August that an independent committee determined that the highest dose—the same as the high dose in the uncontrolled hypertension Phase 2 study—met the main goal of showing a change in average seated systolic blood pressure after 12 weeks.

Treatment-resistant hypertension affects an estimated 13 million to 15 million U.S. patients, CinCor said in an investor presentation. Uncontrolled hypertension is the larger group, affecting between 30 million and 35 million patients in the U.S. If the CinCor drug can only address non-Hispanic or Latino patients with uncontrolled hypertension, the addressable patient population in this group will be cut nearly in half. As the company looks ahead to Phase 3 testing, Freeman said CinCor plans to test the drug in a diverse mix of ethnic and racial groups.

“We will continue to study these populations to make sure we’ve identified those who are most responsive to baxdrostat,” he said.

Deepak Bhatt, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, commented on the CinCor drug’s latest results during the company’s conference call. While he commended the company for conducting a trial with a diverse patient population, he added that the modest size of the Phase 2 study and its multiple subgroups made it hard determine if biological differences based on ethnicity are driving the results. That question should be explored, he said.

“My own feeling though is it’s probably less likely biology that’s explaining this and more likely the sites, specifically, those five sites where the adherence just wasn’t as high,” Bhatt said. “So I think it’s more having to do with sites and adherence at particular sites than it is anything in terms of genetics or even in terms of race/ethnicity.”

One positive note from the failed Phase 2 test is that the drug was well-tolerated by patients. No serious adverse effects were reported in the trial, and the drug’s safety profile was consistent with what was observed in the prior mid-stage test in treatment-resistant hypertension. CinCor plans to meet with the FDA to discuss the Phase 3 path for the drug.

CinCor’s path could keep the company in the hunt along with other companies with aldosterone synthase inhibitors. Mineralys Therapeutics has reached mid-stage testing with MLS-101, a hypertension drug licensed from Mitsubishi Tanabe Pharma Corporation. Philadelphia-based Mineralys, which raised $118 million in financing last June, reported two weeks ago that its drug met main and secondary blood pressure reduction goals of its Phase 2 test in both uncontrolled and resistant hypertension. Damian Pharma is developing its drug candidate DP13 as a treatment for primary aldosteronism, a disorder in which the adrenal glands produce too much aldosterone. In October, the Switzerland-based company presented data showing statistically significant reductions in aldosterone and blood pressure.

CinCor views baxdrostat as a “pipeline in a product.” In addition to uncontrollable and resistant hypertension, the company is evaluating the molecule as a potential treatment for primary aldosteronism and chronic kidney disease. The company expects to report preliminary Phase 2 data in both indications in the second half of 2023.

Public domain photo by Flickr user agilemtkg1

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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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The FDA has approved the first hemophilia B gene therapy, a one-time treatment that addresses a root cause of this inherited disorder and potentially eliminates the need for regular infusions that patients currently receive to prevent bleeding episodes. Removing that economic burden from patients and the healthcare system the comes with a premium upfront price: $3.5 million for a single infusion.

The regulatory approval announced late Tuesday for the CSL Behring therapy covers adults who receive prophylactic infusions or have a history of life-threatening bleeding, as well as those who have repeated and serious spontaneous bleeding episodes. The gene therapy, known in its development as etranacogene dezaparvovec, will be marketed under the name “Hemgenix.”

Hemophilia is a bleeding disorder in which genetic mutations lead to abnormally low levels of clotting proteins. The two most common types of the disorder are hemophilia A and hemophilia B; the latter is the rarer of the two accounting for about 15% of hemophilia patients, according to the FDA. It’s caused by a mutation to the gene that codes for a clotting protein called factor IX (FIX). While many women can be carriers of the disease, they usually have no symptoms. Most of the patients who have hemophilia B and develop symptoms are men. The product’s label state that the therapy is not intended for administration in women.

Without sufficient levels of clotting proteins, hemophilia patients are susceptible to bleeding episodes. Standard hemophilia B treatment includes regular FIX infusions to replace the clotting protein that patients lack. CSL Behring, the King of Prussia, Pennsylvania-based subsidiary of CSL Limited, already markets such therapies, which are made from donated human plasma. But hemophilia B patients require these infusions for life.

Hemgenix is a one-time treatment. The therapy uses an engineered virus to deliver to patients’ liver cells a version of the FIX gene that’s intended to restore production of the deficient clotting protein. The FDA approval is based on an open-label study enrolling 57 adult males ages 18 to 75 with moderate to moderately severe hemophilia B. The main goal was to measure the change in annualized bleeding rate.

Results showed that seven to 18 months after infusion, the average adjusted annualized bleeding rate was reduced by 54% compared to baseline. Furthermore, 51 out of 54 patients, or 94%, stopped the use prophylactic FIX infusions. But the therapy does not completely restore FIX production to the levels of typical healthy human. The average FIX activity of patients in the study was 39% at six months after the infusion; at 24 months, it was 36.7%.

The most common side effects reported in the clinical trial were high levels of liver enzymes, headache, infusion-related reactions, and flu-like symptoms. The FDA said patients should be monitored for infusion reactions and elevated liver enzymes, which can be a sign of liver toxicity. During Hemgenix’s clinical development, a case of liver cancer led the FDA to place pause tests of the gene therapy. An independent inquiry concluded that this cancer was unlikely to be related to the gene therapy, leading to the removal of the clinical hold. The one patient death in the trial was attributed to cardiogenic shock and sepsis that spread from the urinary tract to the kidney—both deemed unrelated to the gene therapy.

Clinical trial data at 18 months were presented earlier this year during the annual meeting of the European Association for Haemophilia and Allied Disorders. The company plans to present updated 24-month follow-up data next month during the annual meeting of the American Society of Hematology.

Like other gene therapies, one-time treatment comes with a premium price. CSL Behring’s $3.5 million list price for Hemgenix, tops the $2.93 million to $2.96 million range in which the Institute for Clinical and Economic Review (ICER), a drug price watchdog group, calculated the therapy would be cost effective. When the report was released earlier this month, it used a $4 million placeholder price to assess Hemgenix. At that price, ICER said the CSL Behring gene therapy becomes cost effective after 8.5 years—if the durability of the treatment holds up that long.

Pricing experts and consultants note that the sky-high cost of gene therapies are pushing pharmaceutical and biotech companies to adopt value-based or outcomes-based agreements. These pacts tie the reimbursement of the therapy to defined goals or outcomes. Bluebird Bio announced such an agreement for Zynteglo, its recently approved gene therapy for the rare blood disorder beta thalassemia. If patients do not achieve and maintain transfusion independence at two years, the Bluebird Bio pledged to refund some of the therapy’s $2.8 million price.

In an emailed statement, CSL Behring said it will also offer commercial payers value-based agreements, though it did not disclose any details about those pacts. Because hemophilia B is a rare disease affecting about 6,000 patients in the U.S. and an even smaller number of those who require FIX therapy, only a small portion of people will be eligible for Hemgenix, the company said. That means Hemgenix’s impact on healthcare systems budgets will be very small. Furthermore, the company contends Hemgenix will save money by reducing the lifetime of costs associated managing the bleeding disorder.

“We are confident this price point will generate significant cost savings for the overall healthcare system and significantly lower the economic burden of hemophilia B by reducing annual bleed rates, reducing or eliminating prophylactic therapy and generating elevated FIX levels that last for years,” CSL Behring said.

In addition to being a first-in-class therapy gene therapy, Hemgenix is also the best-in-class therapy for hemophilia B, William Blair analyst Sami Corwin said in a research note sent to investors Wednesday. The firm’s survey of U.S. physicians who treat hemophilia found that a weighted average of 36% of adult hemophilia B patients would be good gene therapy candidates. That’s less than the weighted average of those classified as having severe or moderately severe disease but in line with the weighted average of patients receiving FIX infusions to prevent bleeding episodes. This latter group could be early adopters of the CSL Behring gene therapy, Corwin said.

CSL Behring acquired Hemgenix two years ago, paying uniQure, $450 million up front. The Dutch company could receive up to $1.6 billion depending on the achievement of milestones.

Photo: Carla Gottgens/Bloomberg, via Getty Images

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For targeted cancer therapy to work, it’s not enough to identify the right targets to hit with a drug. Just as important is selecting the patients appropriate for a given therapy. Scientists at Acrivon Therapeutics say their approach brings advantages over genetic-based patient selection. The Acrivon technology is approaching its first tests in humans with a drug acquired from a big pharmaceutical company. The IPO market, like the weather, has turned cold but Acrivon still found a way to raise nearly $100 million for its clinical trial plans.

Acrivon came close to the nine-figure IPO it wanted, but it had to slash the stock price and sell more shares in order to pull it off. This past week, the biotech offered more than 7.5 million shares for $12.50 apiece, which raised $94.4 million. When Acrivon set preliminary terms for the IPO earlier this month, it planned to offer 5.9 million shares priced in the range of $16 to $18 each.

Watertown, Massachusetts-based Acrivon was able to get closer to the $100 million mark by striking a separate and concurrent deal. Chione Limited, the largest shareholder in the company prior to the IPO, purchased 400,000 shares at the IPO price, raising another $5 million. Acrivon shares now trade on the Nasdaq under the stock symbol “ACRV.”

Matching a cancer drug to a patient is typically done according to genomics. That works when tumors have single driver mutation that causes cells to become cancerous. But Acrivon notes that more than 90% of all human cancers don’t have such mutations. Rather than looking for a genetic target, Acrivon measures proteins that are critical to tumor-driving mechanisms. The company contends this proteomics approach could be applicable to the majority of cancers that do not have genetic alterations in the drug target itself.

“Our founding vision is that proteomic biomarkers enable direct measurement of the disease-driving mechanisms and allow for accurate matching with drug action, independent of underlying genetic alterations,” Acrivon said in its updated prospectus.

The science upon which Acrivon’s technology is based stems from the research of co-founder and CEO Peter Blume-Jensen, whose pharma industry experience includes senior roles at EMD Serono and Merck & Co. In a 2001 article published in the journal Nature, Blume-Jensen and co-author Tony Hunter describe how cancer is driven by dysregulated protein signaling.

Acrivon, whose name is derived from the Greek word for “accurate,” formed in 2018. The company’s tech platform, called Acrivon Predictive Precision Proteomics, or AP3, develops tumor biopsy tests that can be used to match a drug to the patients most likely to respond to it. These tests, called OncoSignature, measure for elevated levels of proteins that a tumor depends on and that are specific to biochemical pathways addressed by a drug. Acrivon has used OncoSignature to guide the development of internally discovered drug candidates that are currently preclinical. For OncoSignature’s first test in a clinical trial, the biotech turned to molecule that stalled in the hands of Eli Lilly.

The Lilly drug, prexasertib, has a long history with multiple stops. Initially developed under a collaboration between Array Biopharma and Icos, the drug joined Lilly via the pharma giant’s $2.1 billion acquisition of Icos in 2007. The heart of that deal was blockbuster erectile dysfunction drug Cialis; prexasertib was still preclinical at the time.

Prexasertib is designed to treat cancer by interfering with a way tumors fix themselves. The rapid and uncontrollable cell growth characteristic of cancer wreaks havoc on cancer DNA. Tumors rely on DNA damage response, a repair mechanism governed by certain proteins. The Lilly drug, which Acrivon has renamed ACR-368, is designed to block CHK1 and CHK2, two proteins that temporarily stop cell replication in order to allow repair of DNA damage. Blocking these proteins prevents those repairs, leading instead to cell death.

No CHK1/2 inhibitors have been approved by the FDA yet. Lilly advanced its CHK1/2-blocking drug to multiple Phase 1 and Phase 2 clinical trials but stopped work on the small molecule in 2019. According to Acrivon’s prospectus, Lilly’s Phase 2 tests in ovarian cancer led to an overall response rate of just 12%. Acrivon believes that by identifying likely responders, its technology can lead to better response rates.

Acrivon was able to obtain pretreatment samples from a subset of ovarian cancer patients who participated in prexasertib trials run by the National Cancer Institute (NCI) and Lilly. According to the IPO filing, a third-party biostatistician reviewed the trial data and OncoSignature scores and found that using the Acrivon test to identify patients appropriate for the therapy boosted the response rate to 47% in the NCI trial 58% in the Lilly study. Acrivon also said the analysis was able to eliminate patients who are less responsive to the drug, which would have spared them from a treatment that would not help them.

Acrivon plans to advance ACR-368 into single-arm Phase 2 studies in ovarian, endometrial, and bladder cancers. Participants in the trials, which the company said could support potential regulatory submissions, will be assigned to subgroups according to their sensitivity to the test drug as determined by OncoSignature.

Acrivon acquired prexasertib in 2021 for cheap. According to the IPO filing, the biotech paid $5 million in cash and issued Lilly shares in the company. Acrivon could pay Lilly up to $168 million in milestone payments linked to the progress of the drug, plus royalties from sales if it reaches the market. The agreement also gives Lilly limited first rights to negotiate the reacquisition of the cancer drug. That right expires 45 days after the completion of certain clinical milestones that are not specified in the IPO filing.

While ACR-368 gives Acrivon an asset ready for a new slate of mid-stage tests, its preclinical programs address other pathways key to DNA damage response. One addresses a protein called WEE1; the other a protein called PKMYT1. There are competitors developing drugs that address DNA damage response. GSK acquired Sierra Oncology largely due to the promise of myelofibrosis drug momelotinib, but that biotech’s pipeline also includes CHK1 inhibitor SRA737. Phase 2 work on adavosertib, a WEE1-blocking small molecule that AstraZeneca licensed from Merck, was stopped this past summer. But others that have reached the clinic with WEE1 inhibitors include Zentalis Pharmaceuticals, Debiopharm, and Impact Pharmaceuticals.

Acrivon’s stock market debut comes nearly one year after it raised $100 million in Series B financing. Prior to the IPO, the biotech raised $119.8 million, according to the filing. Chione is Acrivon’s largest shareholder, owning 18.4% of the company after the IPO. RA Capital Management owns a 7.5% stake. Acrivon reported its cash position was $83.9 million at the end of June. Most of the IPO cash will go toward development of ACR-368. Between $80 million and $90 million is planned for defining the manufacturing processes and product specifications of the drug as well as developing a companion diagnostic, according to the filing.

In time, Acrivon plans to test ACR-368 in other cancers based on drug sensitivity assessed by OncoSignature. Those cancers include human papilloma virus positive squamous cell cancer of the head and neck, as well as anal and cervical cancers. The IPO filing states that the company plans to use some of the new capital to start a mid-stage test in patients with HPV-positive tumors. Another $15 million to $20 million is set aside for completing the preclinical testing leading up to an investigational new drug application for at least one of the company’s preclinical programs. The company will use the remaining cash to continue development of the AP3 technology and for other R&D work. Acrivon expects the cash to support the company into the fourth quarter of 2024.

Photo by Flickr user FutUndBeidl via a Creative Commons license

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With more sophisticated therapeutics comes larger and more complex data sets. The complexity is heightened with the advancements in personalized medicine as it introduces new data points at apheresis (the extraction and infusion of patient blood, cells, tissue and/or regenerative medicinal compounds) and during enhancements of cells and genes.

While data integrity is critical to building confidence in the supply chain and product quality, as well as meeting FDA compliance obligations, many organizations remain highly reliant on spreadsheets, manual data entry, paper records and email. This creates numerous opportunities for error and can result in FDA warning letters, fines or recalls. While data “capture” may start early in biopharmaceutical R&D, oftentimes, a variety of disparate IT systems are installed without a view towards data coherence throughout process development and clinical and commercial manufacturing.

These challenges are compounded by the universal reliance on external partners for significant process development and manufacturing operations.

To attenuate the risks of delayed, incomplete and inconsistent data, biopharma companies must establish a solid data management approach early in product development. Especially for startups that may not have a lot of IT experience or staff, this can be daunting.

The following items should be prioritized in order to better address and mitigate enterprise risks around data integrity and reliability:

  • Creation of a digital data backbone throughout the product and process lifecycle and across internal and external teams, sites and partners
  • Interdepartmental review of Quality and Supply Agreements with CDMOs [contract development and manufacturing organizations] to ensure data visibility, IP ownership and process oversight

Establish a single digital data backbone early

There are new business demands for information to be processed faster. Building a digital data backbone early supports key activities further downstream – late-stage process development, scale-up and tech transfer, and manufacturing where quality assurance and compliance requirements come into the picture.

New digital data systems retain or establish the context and relative importance of data collected from the IT infrastructure. By implementing a cloud-based data backbone, data can be gathered and organized in a central platform without compromising context. It can scale as product and IT infrastructure matures, and remains relevant as it integrates with systems like LIMS [laboratory informatics managements systems], historians, MES [manufacturing execution systems] and eBRs [electronics batch records software], to serve as your single verifiable source of truth for data critical to monitoring process control and conducting analysis and reporting.

With the increasing demand for accelerated tech transfer, FDA filings and commercialization, creating a data backbone early generates significant time and cost benefits: fewer PPQ [process performance qualification] runs, right first time tech transfer, streamlined investigations and production and earlier batch release.

Though a cloud-based data management solution is the first step, companies must also be vigilant when partnering with manufacturers.

Data visibility in quality and supply agreements

With the acceleration of new drug and therapy development, complex manufacturing requirements, and associated capital investments, the growth in outsourcing is predicted to continue for the foreseeable future.

Despite outsourcing manufacturing, the drug owner (sponsor) remains liable for meeting the FDA’s standards for product quality, demonstrating control over the contract manufacturer and the drug manufacturing process, and establishing an inscrutable, high-integrity process, product and quality data set. The near-universal reliance on contract manufacturers, and the FDA’s focus on data integrity issues in drug manufacturing, have generated unprecedented scrutiny into manufacturing operations by the FDA, strategic acquirers and the SEC. As the supply chain continues to expand in complexity, process development and manufacturing, data management is an area that demands new approaches/innovation.

While data integrity challenges can lead to quality and operational issues, they can also create legal risks, such as loss of manufacturing intellectual property and failure to demonstrate control over the CDMO, which can affect the company’s enterprise value.

Although these challenges affect large and small companies alike, data visibility is a key pain point for small biopharma companies, as most are 100% reliant on CDMOs but often lack the expertise and/or negotiation power against well-established CDMOs.

Despite mandates from the FDA for managing their CDMOs – and the manufacturing processes, drug owners struggle to meet these requirements, being physically remote and often lacking IT systems designed for data sharing between owner and contract partners. Failure to meet this requirement can result in the issuance of FDA warning letters. In fact, approximately 50% of all FDA warning letters in 2019 were related to data integrity issues.

Supply agreements must anticipate data needs and emphasize data visibility and ownership of critical information, including process control parameters.

Fortunately, an increasing number of CDMOs realize the compliance burden on their drug sponsors and that the future of biopharma is dependent upon collaboration and visibility in their manufacturing workflows. With state-of-art data management solutions and collaboration with CDMOs, biopharma companies can become more confident in their product quality and more prepared to satisfy strict compliance requirements.

Cloud-based data management solutions help the industry meet its business and compliance challenges. These platforms need to replace traditional data management methods and workflows for biopharma companies and CDMOs that seek competitive advantages.

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Zenas BioPharma is preparing to take its lead drug candidate into a global Phase 3 test and it now has $118 million to finance the clinical research.

The Zenas drug, obexelimab, is being developed as a treatment for IgG4-RD, a chronic inflammatory disease that affects multiple organs. First-line treatment includes steroids, but these drugs can have toxic effects and relapse is common.

Obexelimab is intended to tamp down the activity of B cells, a type of immune cell. The drug is a bispecific antibody. One part of the drug binds to CD19, a protein on the surface of B cells. The other part of obexelimab binds to another immune cell target called FcYRIIB. According to the company, binding to both targets simultaneously mimics a natural antigen-antibody complex that down regulates B cell activity. This approach has potential applications in many autoimmune disorders.

Zenas acquired global rights to obexelimab from Xencor last year, issuing equity to that company as an upfront payment. According to the deal terms, Xencor could receive up to $480 million in milestone payments depending on Zenas’s progress with the drug.

In addition to supporting obexelimab, Zenas said the new capital, a Series B financing, will also go toward advancing other programs into clinical development in 2023. Enavate Sciences led the latest investment in Waltham, Massachusetts-based Zenas. Other new investors in the company include Longitude Capital, Vivo Capital, Rock Springs Capital, Perceptive Advisors, Agent Capital, Pivotal bioVenture Partners and Superstring Capital. Earlier investors Fairmount, Wellington Management, Tellus BioVentures, Quan Venture Fund, and Xencor also participated in the financing

Zenas’s $118 million financing was the biggest biotech financing of this week. Here’s a look at other companies that raised money:

—Bringing computational techniques to the study of secreted proteins, Juvena Therapeutics is developing new drugs for chronic disorders and diseases of aging. Juvena’s lead program is in preclinical development for the muscle disorder myotonic dystrophy type 1 and the Redwood City, California-based startup has raised $41 million to support that drug and others in the pipeline. Mubadala Capital and Horizons Ventures led Juvena’s Series A financing.

—Sensorium Therapeutics emerged with $30 million in funding to develop psychoactive molecules to address mental health disorders. Founded by scientists from Massachusetts General Hospital and Harvard Medical School, Sensorium’s research has produced a lead program, SENS-01, for anxiety and depression. The Boston-based biotech said it expects to begin preclinical research that could support an investigational new drug application in 2023, laying the groundwork to reach clinical testing by early 2024. Santé Ventures led Sensorium’s Series A financing.

—New investors pumped money into Lipidio Pharmaceuticals, extending the biotech’s Series A round of financing to more than $20 million. San Diego-based Lipidio is developing drugs for metabolic and skin disorders. Lead drug candidate GDD3898 is in development for treating acne, sebaceous hyperplasia, obesity, and Prader-Willi syndrome. The company said it expects to complete three early-stage studies of the drug by the end of this year, laying the groundwork for data analysis and a Series B financing planned for the first quarter of 2023.

—Blood transfusion technology company Hemanext raised $18 million. The Lexington, Massachusetts-based company has CE mark certification in Europe for a red blood cell processing and storage system and is working to expand its presence into additional European markets in 2023. Hemanext described the latest financing as the first close of its Series B round. The company says it has raised about $130 million total to date.

—Neuroscience company NRG Therapeutics closed £16 million in financing to continue development of small molecule drugs that penetrate the brain to potentially slow or halt neurodegeneration. The drugs of the Stevenage, England-based company target mitochondria, the powerhouses of cells. The Series A round of financing was led by Omega Funds. NRG plans to use the capital to advance its molecules through the preclinical research needed to support an investigational new drug application.

Picture: Feodora Chiosea, Getty Images

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