Medical Innovation Exchange

Annalee Armstrong

Roche, Lilly push back against CMS painting their Alzheimer’s meds with the same brush as Biogen’s Aduhelm

In a rare moment of solidarity among fierce competitors, Biogen’s peers Roche and Eli Lilly are rallying behind the company’s troubled Alzheimer’s disease therapy, Aduhelm, in an effort to change the Centers for Medicare and Medicaid Services’ restrictive ruling against monoclonal antibodies for the condition.CMS just closed a comment period on a proposal to limit Medicare coverage of Aduhelm to only patients enrolled in approved clinical trials. If the decision passes as currently written, the ruling would also apply to other monoclonal antibodies, or mAbs, in development that target amyloid like Aduhelm, including those by Lilly and Roche’s Genentech.
Lilly’s Brandy Matthews, medical launch leader for the company’s candidate donanemab, urged the agency to consider mAbs individually based on the evidence for each candidate, rather than restricting all amyloid-clearing therapies in the class. She advocated for the one drug that has already been approved, Aduhelm, and those to come to be covered for the populations studied in their respective clinical trials. Any future changes in covered patient populations can then be informed by the FDA’s labeling updates or based on evidence presented in peer-reviewed published studies.

“We urge CMS to ensure that its coverage decision does not intentionally or unintentionally limit access to future therapies,” Matthews said.
RELATED: Biogen, Eisai strike back against CMS’ stifling Aduhelm coverage proposal
CMS’ proposal to limit coverage also got plenty of support, however. Some argued that the therapy was too expensive for full coverage considering the FDA approved it without definitive evidence of efficacy. Others said that patients need access to existing treatments now, but coverage should be restricted to ensure patients and their caregivers have a sound understanding of the benefits and risks. Still more commenters urged CMS to not cover Aduhelm and other mAbs at all and that the FDA should not have approved it in the first place.
The Indianapolis Big Pharma said last week during an earnings call that the completion of an accelerated approval application for donanemab would be pushed back to later this year in light of the CMS decision. The company is hoping to have some data on clinical efficacy available to support the application.
Matthews urged CMS to examine Lilly’s therapy based on the evidence presented with the application for accelerated approval, rather than lumping it into a category and denying full coverage automatically.
Genentech echoed the concerns in support of its candidates gantenerumab and crenezumab. Similar to Lilly, Genentech wants to deliver on efficacy data to prove once and for all that the drugs work. Both candidates are in various stages of clinical testing, with gantenerumab leading the way. A critical readout for the therapy is expected in the second half of this year.
“We believe that by including anti-amyloid therapies still undergoing phase 3 clinical trials within the scope of this policy, CMS is jeopardizing individuals’ access to products that may be approved in the future and that might be appropriate for their specific treatment needs, without even considering the evidence for those products,” wrote Genentech’s David Burt, executive director of federal government affairs.
RELATED: Completion of Lilly’s Alzheimer’s submission slips out of Q1 after CMS’ Aduhelm decision
Genentech also noted that limiting coverage to just approved clinical trials will hamper the development of real-world evidence, which can inform future innovations. Burt argued that this will set back advancements in research and clinical practice in Alzheimer’s. Biogen and Eisai similarly argued this point in their comments.
Burt also noted that the restrictions will disadvantage people living in more rural areas or underserved communities. The types of trials that CMS is proposing to limit coverage to are traditionally conducted in urban academic medical centers that have long struggled to address diversity in clinical trials.
Eisai and Biogen also argued against the broad ban on the anti-amyloid mAbs class, both in an effort to rescue Aduhelm and for their next Alzheimer’s candidate. 
“In its current proposal, CMS would hold FDA-approved therapies for Alzheimer’s disease to a different standard than it has previously applied to therapies in any other disease states, including other accelerated approval drugs,” Biogen said.
Also backing up the individual Big Pharmas were the industry groups PhRMA and BIO, which represent pharmaceutical companies and biotechs, respectively.
RELATED: ‘What it takes’: Beyond the headlines, women are pushing groundbreaking new Alzheimer’s treatments forward
“It is imperative that CMS does not worsen existing disparities in treatment for Alzheimer’s by limiting access to this class of treatments,” argued PhRMA, noting that the disease disproportionately affects Black Americans and Hispanics.
BIO, meanwhile, expressed a long-standing concern about CMS’ push to restrict coverage of new FDA-approved drugs and “impose new coverage barriers.”
CMS is expected to issue its final ruling in April. 

Cassava scores a win as FDA declines to intervene in petition to stop its Alzheimer's drug trials

Cassava Sciences has chalked up one win in an ongoing battle over the integrity of its clinical trials for Alzheimer’s disease. The FDA is declining to intervene in a citizen petition’s plea to halt ongoing clinical trials of the company’s drug, simufilam, saying the petition was not the appropriate venue for such a complaint.That still leaves a federal investigation from the U.S. Securities and Exchange Commission and other unnamed government agencies, which are looking into allegations that the biotech manipulated data for the experimental Alzheimer’s med called simufilam.
Cassava CEO Remi Barbier called the FDA’s decision “very welcome but not surprising,” in a statement Thursday.

“We said from the outset that the allegations are false. I think the message may be that the FDA’s citizen petition privilege is not to be trifled with by stock market participants,” Barbier said.
RELATED: Cassava CEO, ‘dazed and confused,’ takes to biotech defense handbook by blaming short sellers for woes
The original complaint was filed in August by a lawyer representing short sellers of Cassava’s stock, with supplemental requests added through the year. The group detailed “grave concerns about the quality and integrity of the laboratory-based studies surrounding this drug candidate and supporting the claims for its efficacy.”
Simufilam does not attempt to clear amyloid from the brain like other common Alzheimer’s treatment in development but instead tries to stabilize a scaffolding protein called filamin A. The petition claimed that no lab has confirmed a link between filamin A and Alzheimer’s disease or its effect on models for the disease. The petitioners further alleged data anomalies and manipulation including image alteration in Cassava’s clinical work.
While the FDA said it wouldn’t intervene in the petition’s request to halt ongoing clinical trials, the agency was clear that it was not ruling on the allegations.
“We take the issues you raise seriously. Please note that your petitions are being denied solely on the grounds that your requests are not the appropriate subject of a citizen petition,” wrote Patrizia Cavazzoni, M.D., director of the FDA’s Center for Drug Evaluation and Research.
RELATED: Cassava ploughs on with 2nd phase 3 trial of Alzheimer’s med despite federal investigation
Cassava is enrolling mild-to-moderate Alzheimer’s in two phase 3 simufilam trials.
As for the government inquiries, Cassava reported in a November 2021 filing to the SEC that the company has received requests from “certain government agencies” for corporate information and documents. The agencies have not informed the company of any wrongdoing, according to the filing. 

Rivus throws down mid-stage liver fat data on quest to climb NASH mountain

Considering NASH drug development has stumped companies big and small, can newcomer Rivus Pharmaceuticals move the needle?The Charlottesville, Va.-based company hopes so, and is out today with data on its lead candidate showing a reduction in liver fat, a key hallmark of NASH, or non-alcoholic steatohepatitis. The results also provided some evidence that suggests improvements in metabolic parameters related to Type 2 diabetes, a type of heart failure and the tricky liver disease NASH.
The drug prospect, called HU6, met the primary endpoint of reducing liver fat in a phase 2a study of patients who were obese with elevated liver fat. Secondary goals included different measures of fat loss. The endpoints were achieved while conserving skeletal muscle mass. Patients also saw improvements in markers of insulin resistance and inflammation, according to Rivus.

The company believes that HU6 could help address the root causes of metabolic diseases by reducing liver fat, especially since the results occurred in a relatively short timeframe of eight weeks.
RELATED: Rivus’ fat-trimming therapy nabs $35M to harness our own biology against a host of diseases
Rivus said that the therapy achieved reductions in liver fat ranging from 33% to 40% depending on the dose. Participants lost an average of six pounds during the study, but participants who had elevated blood glucose saw even greater reductions in weight and fat. These patients lost an average of 10 pounds.
As for safety, HU6 was well tolerated with no serious adverse events recorded. One patient in the low-dose group discontinued due to diarrhea, but no discontinuations were seen in the high-dose group.
With the results in hand, the company can now consider whether reducing visceral and organ fat can benefit patients with cardiometabolic diseases, Rivus’ Chief Scientific Officer Shaharyar Khan, Ph.D., said.
The biotech plans to continue with the HU6 clinical program through the first half of the year, including a phase 2a study in heart failure with preserved ejection fracture. A phase 2b study in type 2 diabetes and NASH will come next.
RELATED: Madrigal’s NASH prospect clears first phase 3 test, raising hopes it can magic up positive pivotal efficacy data 
NASH has stymied some of the top drugmakers in the world. Bristol Myers Squibb in November shelved a mid-stage asset in the disease after lackluster results. But Big Pharma still wants in on this potentially lucrative market. GlaxoSmithKline just put up to $1 billion on the line in a pact with Arrowhead Pharmaceuticals to develop the NASH candidate ARO-HSD.
A couple small biotechs have kept the lights on in NASH. Madrigal and 89bio both reported some success with their candidates in January. To join that group, Rivus will need to see that phase 2b through.
Rivus emerged in July of last year with a $35 million series A to tackle a host of metabolic disorders. 

Arrowhead ‘changing horses’ for ENaC pulmonary program as phase 1/2 asset shelved

Arrowhead Pharmaceuticals is ditching a pulmonary drug after it failed to hit the mark in a phase 1/2 trial last year. But the biotech is filling up its quiver with at least two more prospects in the program as a replacemenExecutives reported the pipeline changes in the company’s fourth-quarter earnings (PDF) Wednesday afternoon. President and CEO Chris Anzalone, Ph.D, said Arrowhead is making progress on the ENaC target, or epithelial sodium channels, which is a potential pathway in cystic fibrosis to rehydrate airway surfaces and improve the work of mucus in the body.
But that progress has not been seen with ARO-ENaC. The company paused a phase 1/2 cystic fibrosis study last year after rats in a preclinical study showed unexpected lung inflammation. Anzalone said Arrowhead “will likely not continue” with the candidate.

Instead, Arrowhead has two or three next-gen compounds in the works to fill the gap. These candidates “appear to have favorable pharmacologic properties compared to ARO-ENaC,” according to the CEO.
RELATED: Arrowhead slams brakes on early-stage cystic fibrosis study after rat study triggers lung inflammation concerns
“So, we are likely changing horses in the ENaC program, but we have not yet settled on which new horse,” Anzalone said.
The decision to abandon ARO-ENaC was not a surprise to RBC Capital Markets analysts, who pointed out the discontinuation in a note to clients.
Arrowhead’s James Hamilton, M.D., senior VP, discovery and translational medicine, said the preclinical inflammation seen in rats has since been confirmed in nonhuman primates as well.
Hamilton said the problems could have stemmed from an overdose in the preclinical animal studies, which could have been tweaked to find a cleaner toxicity profile for future trials.
“That could provide a faster path back to the clinic, but we decided that the better long-term path is to focus on next-generation ENaC candidates,” he said.
RELATED: Arrowhead can see the Horizon with $700M biobucks pact for an early RNA gout med
Arrowhead plans to file two new clinical trial applications with the FDA for ARO-RAGE and ARO-MUC5AC in various muco-obstructive and inflammatory pulmonary conditions over the next quarter, according to the CEO. Preclinical data is expected at the American Thoracic Society meeting in May.
Hamilton said that these drugs have been tested at a lower exposure level than the first-generation ENaC program and appear to be more potent. The expectation is that less of the drug can be used with less frequent dosing.
A third application is also expected by the end of the year in an unnamed target and disease area.

Pfizer accuses former employees of 'treachery' in stealing trade secrets to form Regor Therapeutics

Pfizer has accused two former employees who went on to form a new biotech of stealing “the hard work” of the Big Pharma’s own scientists for a diabetes and obesity program, according to a lawsuit filed Wednesday.“Instead of carrying out their ethical and contractual responsibilities as Pfizer employees, they decided to steal the hard work of Pfizer’s scientists and clinicians for their own profit and gain,” the complaint says of former employees Min Zhong and Xiayang Qiu.
The complaint alleges that Zhong and Qiu set up Regor Therapeutics while still employed at Pfizer, meeting with international financial backers to secure funding. Zhong and Qiu also set up a second company called QILU Regor Therapeutics.

The company is focused on metabolic diseases and signed a biobucks deal with Eli Lilly in December worth $1.5 billion. While the focus of that pact was not revealed at the time, Lilly is well known for its diabetes franchise and is testing one of those therapies as an obesity treatment. Pfizer said in its complaint that the Lilly deal includes a license for Regor’s small-molecule GLP-1R agonist patents.
RELATED: Eli Lilly pens $1.5B biobucks pact with China’s Regor for metabolic disease work
Pfizer said the defendants stole trade secrets and confidential information for weeks before giving notice that they would be leaving the company. The complaint said a confidential document, stripped of Pfizer confidentiality marks, was uploaded to a personal account two months before Zhong and Qiu left. They later used this information in a new presentation “about a revolutionary new diabetes and obesity drug” that Pfizer said detailed confidential information from its GLP-1 program.
“The Pfizer trade secrets and confidential information that Qiu and Zhong stole essentially gave defendants the playbook and the critical underlying science and data to develop their own supposed diabetes and obesity treatment, an unlawful head start that saved defendants significant money and years of development time,” Pfizer said.
Within months of founding Regor, Pfizer said the defendants filed for patent protection for a treatment “strikingly similar” to Pfizer’s diabetes and obesity treatment. The company says that Qiu, who serves as CEO at Regor, and Zhong, who is chief operating officer, could not have developed such a treatment in such a short amount of time without the theft.
The alleged theft was discovered after a forensic analysis of Qiu’s and Zhong’s Pfizer accounts and devices. Zhong’s Pfizer-issued iPhone has not been recovered.
RELATED: After Wegovy win, Novo Nordisk lines up EraCal for obesity research collaboration
“Pfizer conducted its analysis after it first suspected defendants’ treachery upon publication of Regor’s patent application that claimed the fruits of Pfizer’s yearslong research,” the complaint said.
Pfizer notes that Regor has managed to “entice” Lilly into signing the billion-dollar-plus deal.
The complaint alleges that Qiu and Zhong misappropriated trade secrets in violation of the Defend Trade Secrets Act as well as Connecticut trade secret laws.
The New York pharma has two GLP-1 candidates under development for diabetes and obesity. Danuglipron is in phase 2 development while PF-07081532 is in phase 1, according to Pfizer’s pipeline.
“Pfizer’s small molecule GLP-1 receptor agonist technology is highly promising from both a clinical and commercial perspective—and the trade secrets and confidential information behind it would also be highly lucrative to a competitor looking to avoid Pfizer’s substantial investment while reaping the commercial benefits,” the complaint said.
RELATED: ADA: Eli Lilly’s next-gen GLP-1 moves the needle in early-stage diabetes ahead of FDA filing
According to Regor’s leadership page and the complaint, Qiu served as executive director of structural biology at Pfizer-Connecticut, where he led as many as 60 scientists through drug discovery efforts. His group contributed to 29 clinical candidates. Qiu also served on expert review panels for the National Institutes of Health.
Zhong spent 19 years in Pfizer’s R&D organization, most recently as director of pharmacokinetics, dynamics and metabolism (PDM) and head of its external research solutions group, according to the complaint. In that role, he was responsible for business development for Pfizer’s worldwide R&D external research portfolios as well as scientific/compliance oversight for the PDM group’s regulatory submissions.
Both were working on the GLP program before their departure from Pfizer in 2018, according to the complaint.
“Zhong and Qiu could have continued to build on this important, life-saving work at Pfizer for years to come, but they made a different choice: to take Pfizer’s trade secrets and confidential information unlawfully to launch a competing company,” according to the complaint.
A request for comment sent to Regor was not returned as of publication.

Gilead's CD47 clinical hold expands as CEO O'Day expresses 'sense of urgency' in getting trials back on track

Gilead revealed that a partial clinical hold for its CD47 targeted cancer hopeful is larger than originally thought.Last week, the California-based biotech shared that a handful of trials for magrolimab in combination with azacytidine had been placed on a partial clinical hold because of an “apparent imbalance” in adverse reactions seen in the study arms. The hold applied to five studies, ranging from early- to late-stage development for myelodysplastic syndrome (MDS), acute myeloid leukemia and myeloid malignancies, including the phase 3 Enhance trials. 
As of the Jan. 25 announcement, six ongoing phase 2 trials were not subject to the hold, including two studies for diffuse large B-cell lymphoma and multiple myeloma. 

But Gilead disclosed (PDF) in the fine print of the pharma giant’s fourth-quarter earnings presentation Tuesday that those two studies are indeed subject to the hold, bringing the total number of affected trials to seven. According to the slide presentation, the “FDA placed partial clinical holds on trials evaluating magrolimab in combination with azacitidine as well as the fully enrolled DLBCL and MM study.” These two studies were not combining magrolimab with azacytidine.
RELATED: Gilead’s $4.9B oncology bet hit with partial clinical hold, forcing pause of pivotal trials and raising doubts about CD47
Chief Medical Officer Merdad Parsey, during a Tuesday earnings conference call. referred to the changes as a “subsequent partial clinical hold” for the two studies. The troubles arose from a review of a preliminary dataset that suggested an apparent imbalance in suspected unexpected serious adverse reactions identified in the treatment groups in the phase 3 trial in high-risk MDS, according to Parsey.
Enrollment in the MM study had not really gotten underway yet, which Parsey believes may have been a consideration for the FDA. The DLBCL study, however, had been fully enrolled.
Patients already enrolled are clear to keep taking magrolimab, and Gilead is also maintaining a compassionate use program for the therapy. 
Parsey also said that Gilead is abandoning a phase 1b single arm study in higher-risk MDS because of regulatory feedback. This indication “no longer has a viable path to submission,” he said. Data from the 1b will be released at an upcoming scientific meeting.
The focus will continue to be on the much more advanced Enhance studies, which are for patients with MDS and two types of AML. Patients in Enhance “have a very high unmet need” and are typically quite sick, according to Parsey. Median survival for these cancers is one to three years on existing standard of care.
RELATED: Gilead taps brakes on $4.9B bet after rival’s failure
“I can tell you that we feel that these are temporary challenges right now, and we’re going to work through resolving it as quickly as possible,” Parsey said. “I don’t think these challenges really shake our confidence for the portfolio overall, and our overall strategy hasn’t changed.”
Later in the conference call, CEO Daniel O’Day and CFO Andrew Dickinson expressed confidence in Gilead’s overall oncology program in light of the clinical hold.
“We have obviously a lot of patients on magrolimab. They continue to be served by magrolimab. So we have a sense of urgency in working with the agency around this,” O’Day said.
To respond to the FDA request, Gilead is gathering safety information, which will be shared with the FDA and the data monitoring committee. Parsey and O’Day promised to share the outcome of the safety review as quickly as possible.
RELATED: Gilead’s COVID-19 antiviral Veklury blew past sales estimates in late 2021 as omicron surged, vaccinations lagged
“We have complete confidence in where we’re going, and we don’t expect to change our business development strategy as a result of any of the recent developments,” Dickinson said. “We’re incredibly pleased with what we’ve put together, and nothing that’s happened recently has changed that in any way.”
Magrolimab is an anti-CD47 antibody that Gilead acquired through the $4.9 billion takeover of Forty Seven.

Anavex touts 'very large' phase 3 win for Rett syndrome drug—2 weeks after moving study's goalposts

Anavex Life Science’s press release touting a phase 3 win for a Rett syndrome drug read very much like the famous doge meme that took the internet by storm several years ago. The company claimed “very large” and “large” wins on the main and secondary endpoints.There’s just one problem. The company changed the trial from a phase 2 to a phase 3 and edited those endpoints just 14 days ago. Very wow.
The New York biotech touted the late-stage win Tuesday morning for Anavex2-73, or blarcamesine, in Rett syndrome, a genetic neurodevelopmental disorder that occurs mostly in girls and causes severe impairments in speech, mobility, breathing and other aspects of life.

Anavex2-73, a once-daily oral liquid treatment, was being tested in the phase 3 Avatar trial in adult female patients. Anavex said the therapy beat placebo on the main and secondary goals. The primary endpoint was a dose-dependent change on a rating scale of Rett syndrome behavior, which evaluates patients’ neurobehavioral symptoms related to quality of life. These measures include general mood, breathing problems, hand behaviors, repetitive face movements, body rocking and more.
RELATED: Anavex’s neuro drug slows decline in Parkinson’s disease as it boosts levels of its biomarker
On this measure, Anavex’s therapy spurred a “statistically significant and clinical meaningful improvement” of 72.2% compared to 38.5% in the placebo arm, the company said. This effect size, according to Anavex, was “very large.”
The secondary endpoints relied on a different scale for rating anxiety and emotional behavior in Rett patients. Anavex said that 52.9% of patients taking Anavex2-73 saw improvement compared to 8.3% on placebo. This effect was deemed “large” by Anavex.
So let’s back up to what Anavex was originally studying. According to the FDA’s clinical trials database, the trial was edited beginning Jan. 18 from a phase 2 to a phase 3—a major advancement that puts the therapy closer to registration with the FDA.
But the more material change was to those endpoints. Before the edits, Anavex was evaluating Anavex2-73’s efficacy using a main goal of plasma concentration at seven weeks and the pharmacokinetic activity of the drug. These goals are crucial to determining how a drug works in the body.
Endpoints can certainly be changed once a trial has already commenced. But introducing goals that were not prespecified can introduce bias into the study and compromise scientific integrity. Any changes should be made carefully—and done independently to any data that has already been acquired in the study.
RELATED: Novartis dumps Rett gene therapy caught up in Zolgensma scandal in cull of pipeline prospects
The new goals similarly evaluated patients after seven weeks on the study drug. What’s unclear is what data Anavex had in hand when the endpoints were altered. The study first began in May 2019, and the primary completion is listed as September 30, 2021, on the clinical trials database.
The pharmacokinetic measures and plasma concentrations slid into the secondary goals, and the anxiety assessment was added. The new main goal is the drug exposure-dependent response on the Rett behavior scale.
Anavex also altered a secondary endpoint, which was originally looking for a change from baseline to the end of treatment on a scale measuring improvement. This was revised to measure improvement based on the drug’s exposure-dependent response. The number of participants was also upped from 33 to 36 during last month’s changes.
The company did not report how the drug fared on the original main endpoint in the Tuesday release. Anavex shares plunged 18% to $10.70 as investors sorted through the confusing news and considered the impact of the trial changes. Investors questioned whether the new goals were a meaningful way to show Anavex2-73’s effect. 
Based on the results of the now-phase 3 study and an earlier phase 2, Anavex plans to engage with the FDA about an approval pathway for Anavex2-73. The therapy has fast track, rare pediatric disease and orphan drug tags from the FDA, which means it could be up for an accelerated approval—if the agency is fine with the last-minute trial changes.

Gamida Cell readies stem cell transplant therapy for FDA submission but seeks strategic partners amid staffing cuts

Gamida Cell is initiating a rolling FDA submission for the blood cancer treatment omidubicel, but it is looking for a little help from a strategic partner and slashing staff to get it across the finish line.The submission is expected to get underway in the first quarter and be completed by the end of the half, the company said in a Monday morning release. Omidubicel is being developed as an off-the-shelf bone marrow stem cell transplant for patients with blood cancers. Gamida Cell said that the rolling submission was cleared after positive feedback arrived from a Type B meeting with the FDA. These meetings can be held for therapies that have received a breakthrough therapy designation, like omidubicel.
In November 2021, the FDA asked for more data on Gamida Cell’s manufacturing facility before the submission could move forward. The agency specifically asked for a comparison of omidubicel from the manufacturing plant with records from other facilities, which were used to produce the drug for the company’s phase 3 study.

The biotech reported last year that omidubicel showed benefits over umbilical cord blood and met the main goals of its registrational trial.
The submission may be underway, but to get the drug onto the market, Gamida Cell is seeking strategic partners for commercialization in the U.S. or globally. 
RELATED: Novartis-backed Gamida’s approval plans for cell therapy hits a snag with FDA asking for manufacturing data
At the same time, Gamida Cell is reducing operating expenses by slashing 10% of its staff and delaying planned hirings and spending in 2022. These actions are expected to extend the biotech’s cash runway into mid-2023, a timeline that matches with a potential omidubicel launch.
And in other news, Gamida Cell said that it is also working on addressing concerns the FDA raised that led to a clinical hold for GDA-201 as the biotech was seeking authorization to run human trials. The biotech first mentioned the clinical hold in October 2021. While a phase 1/2 was previously planned for the end of 2021, Gamida Cell now hopes to start the follicular and diffuse large B-cell lymphoma study sometime this year.
Gamida Cell ended 2021 with $96.1 million in cash and cash equivalents, according to the release. The companies shares were up a few percentage points at $2.99 apiece as the markets opened on Monday morning, compared to a prior close of $2.93. 

Gilead tags along again to support cell therapy biotech Kyverna in $85M fundraising

Gilead Sciences has tagged along on Kyverna Therapeutics’ journey as a startup since the beginning, and, now, the Big Pharma has helped stock up the cell therapy biotech in an $85 million financing round to prepare for a launch into the clinic this year.Leading the series B financing was Northpond Ventures, but Kyverna also attracted investment from RTW Investments, Vida Ventures and others. Another name that sticks out on the list is Intellia, which just signed a deal with Kyverna to develop therapies for autoimmune diseases using the gene editing biotech’s CRISPR/Cas9 platform.
Kyverna, which focuses on autoimmune and inflammatory diseases, will use the funds to advance KYV-101 into the clinic for diseases such as lupus nephritis, systemic sclerosis and inflammatory myopathies. KYV-101 is an anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy that has been developed for use in B-cell-driven autoimmune diseases. The therapy is expected to hit the clinic in the first half of this year.

The funds will also help with Kyverna’s recent Intellia partnership. Kyverna said proceeds will support development of KYV-201 in B-cell-driven autoimmune diseases, using the biotech’s CD19 CAR-T construct and Intellia’s ex vivo CRISPR/Cas9-based allogeneic platform. The companies did not detail the financial arrangements behind the partnership when it was announced earlier this month.
RELATED: Intellia bags option on autoimmune CAR-T prospect, handing Kyverna rights to use CRISPR tech to create off-the-shelf cell therapy 
Finally, Kyverna will work on its synReg T-cell platform to engineer synthetic versions of regulatory T cells, which suppress immune responses in the body.
Kyverna will pick up a new board member from the financing, Northpond Ventures Director Shaan Gandhi, M.D., while RTW Senior Analyst Chris Liu, Ph.D., will join as board observer.
The biotech launched in 2020 with a $25 million series A. At the time, the company announced a strategic partnership with Gilead to develop engineered T-cell therapies for autoimmune diseases. Gilead made an upfront payment of $17.5 million, with an additional $570 in development and commercialization milestones possible for Kyverna down the line. 

Pfizer, BioNTech launch trial for potential omicron-busting vaccine

Pfizer and BioNTech are launching a new clinical trial to test a potential omicron-busting COVID-19 vaccine.The new vaccine will be included in a three-cohort study that will also examine different regimens of the companies’ existing COVID-19 shot, Comirnaty, according to a Tuesday press release. 
This new trial is part of Pfizer and BioNTech’s efforts to find a solution for omicron, which has caused the efficacy of existing shots and some antiviral antibody medications to dip. The companies announced in December that lab-based studies suggested three Comirnaty doses were able to neutralize omicron, but, with only two doses, there was a 25-fold decrease in neutralizing antibody levels against the new variant compared to the original variant that the vaccine was designed against.

“Vaccines continue to offer strong protection against severe disease caused by omicron. Yet, emerging data indicate vaccine-induced protection against infection and mild to moderate disease wanes more rapidly than was observed with prior strains,” said BioNTech CEO and co-founder Ugur Sahin, M.D.
The goal is to create a vaccine that protects against omicron just as the earlier vaccines did with other strains but with a longer duration of protection, according to Sahin.
RELATED: Does the world need more COVID-19 vaccines? These companies think there’s still room for improvement
Pfizer has promised to roll out variant-based vaccines quickly, but some experts say it’s too late to bother with this current wave that’s sweeping the world.
Instead, the next generation of vaccines need to be pan-variant and go after parts of the virus that do not mutate as easily—like the spike protein, which is a hallmark of the SARS-CoV-2 virus and the main target for many vaccines but also sees a number of mutations with each variant.
For now, Pfizer and BioNTech will test the omicron-based vaccine in 1,420 healthy adults from 18 to 55 years old. Some participants will come from the companies’ ongoing phase 3 booster study.
“While current research and real-world data show that boosters continue to provide a high level of protection against severe disease and hospitalization with omicron, we recognize the need to be prepared in the event this protection wanes over time and to potentially help address omicron and new variants in the future,” said Pfizer’s Kathrin Jansen, Ph.D., senior vice president and head of vaccine research and development, in a statement.