Medical Innovation Exchange

FDA

Galapagos halts lupus CAR-T program, confirms 100 layoffs so far this year

Galapagos has never been afraid of reworking its pipeline or workforce to face the future. 2022 saw the Belgian biotech pivot to CAR-T therapies and then drop its kidney disease and fibrosis programs—the latter move coinciding with laying off 200 employees.
While last year was less disruptive for Galapagos, it appears the pace of change has ramped back up in 2024. In its full-year earnings report, the company revealed that the 100 layoffs hinted at back in October as a way to “streamline” operations have now taken place.

These roles were culled from “across the Galapagos organization” since the start of the year and were aimed at aligning with “Galapagos’ renewed focus on innovation,” the company said.

Galapagos also used the earnings report to disclose that it has decided to halt work on its CD19 CAR-T candidate aimed at refractory systemic lupus erythematosus. The release was light on details for the move, with Galapagos only ascribing the pipeline change to “strategic reasons.”

Back in November, Galapagos reported that “further progress” had been made in preparing to launch a phase 1b study of the CAR-T therapy, dubbed GLPG5101, in patients with refractory systemic lupus erythematosus. But there have been no updates since.

The biotech has also been testing GLPG5101 in patients with relapsed/refractory non-Hodgkin lymphoma. The company shared early data from phase 1 and 2 trials of the CAR-T therapy in this indication at the American Society of Hematology general meeting in December, claiming the “encouraging safety profile” and initial efficacy data showed “the potential of our CAR-T pipeline beyond these initial indications.”
GLPG5101 isn’t the only candidate Galapagos was testing in systemic lupus erythematosus, however. The company has a selective tyrosine kinase inhibitor called GLPG3667 in a phase 2 trial for the autoimmune condition.

Elsewhere, the company has expanded its remit this year, kicking off 2024 with a $27 million upfront deal to use BridGene Biosciences’ chemoproteomics platform to discover new small molecules for cancer. When announcing in October that the once-promising JAK inhibitor Jyseleca would be transferred to Italy’s Alfasigma, Galapagos suggested that on top of the roughly 400 employees that would move with the drug, another 100 positions would be trimmed at some point.

The company still has plenty of money at hand. Galapagos entered the new year with 3.7 billion euros ($4 billion), which Chief Financial Officer and Chief Operating Officer Thad Huston described in yesterday’s earnings release as “a strong financial position.”
“We will continue to execute on business development opportunities and invest in our pipeline to drive value for all our stakeholders,” Huston added.

GSK, Vir end flu drug alliance, removing key piece of $345M pact

GSK is walking away from a core piece of its $345 million bet on Vir Biotechnology. The partners have ended their collaboration on anti-influenza antibodies, freeing Vir to “actively” pitch the candidates to other companies while continuing to work with GSK on different respiratory pathogens.
Vir partnered with GSK on flu three years ago. The Big Pharma paid $225 million upfront and invested $120 million in Vir to collaborate on drugs to prevent and treat flu, as well as to expand a hunt for targets associated with respiratory viruses and develop antibodies against up to three other pathogens. GSK picked up an option to license the flu candidate VIR-2482 for $300 million as part of the deal.

The likelihood of GSK exercising that option plummeted in July, when Vir reported a phase 2 flop, but the collaboration kept going. That changed this week when, with the three-year research agreement coming to an end, GSK and Vir terminated the influenza portion of their collaboration.

“Vir retains sole rights to continue advancing our investigational therapies for influenza. With that in mind, we are actively pursuing external partnership opportunities for our next-generation influenza A and B antibodies and [antibody-drug conjugates],” Vir CEO Marianne De Backer, Ph.D., said on an earnings call with investors Thursday.

The biotech gave up on VIR-2482 in the aftermath of the phase 2 failure but expects to file to run a trial of its next crack at the flu virus in 12 to 24 months. Vir believes the follow-up prospect, the neuraminidase targeting antibody VIR-2981, has the attributes to succeed where its predecessor failed.

On the call with investors, Vir Chief Medical Officer Phil Pang, M.D., Ph.D., highlighted three ways in which the drug candidate is differentiated from the failed molecule. “It targets both flu A and B, it’s more potent than ‘2482 and it has a derisked mechanism of action, by targeting the neuraminidase enzyme,” Pang said. 
Earlier this week, Vir revealed Pang will step down as CMO at the end of March to spend more time with his family. The biotech is now looking for Pang’s replacement. De Backer told investors Vir has “received a flood of inquiries” since it shared news of the upcoming vacancy and provided details of the criteria for choosing the next CMO.
“What is going to be really critical is for someone to have a proven track record in advancing therapies through phase 3 and having experience bringing therapeutics all the way to market. We’re also looking for someone who has a really in-depth understanding of the evolving regulatory landscape, deep insights in how to use data and big data for insights into clinical development,” De Backer said.

Chutes & Ladders—AbbVie appoints successor for CEO Rick Gonzalez

 Welcome to this week’s Chutes & Ladders, our roundup of hirings, firings and retirings throughout the industry. Please send the good word—or the bad—from your shop to Max Bayer or Gabrielle Masson, and we will feature it here at the end of each week.  

AbbVie names CEO successor

AbbVie
Look, we don’t want to say that the Chutes & Ladders team predicted AbbVie’s new CEO, but … we were onto something. The company formally announced that President and COO Robert Michael will succeed Rick Gonzalez as CEO, ending a good bit of speculation after the current leader teased plans to hand off duties months ago. In June 2023, COO duties were added to Michael’s responsibilities, prompting the C&L team to ever-so-wryly suggest he may be the one. And voila. 

Robert Michael
(AbbVie)

Jokes aside, other signs seemed to point to Michael, with Gonzalez going so far as to explicitly say on the company’s latest earnings call that the board was preparing an internal candidate. 
The official handoff happens July 1, at which point Michael will also join the company’s board. Gonzalez’s departure marks the end of an 11-year tenure at the Chicago-area pharma, marked by Humira’s reign. Fierce Pharma 

Gilead CEO set to lead top pharma lobbying org 

PhRMA
Gilead CEO Daniel O’Day is the new chair of the Pharmaceutical Research and Manufacturers of America (PhRMA), one of the leading lobbying organizations for the pharmaceutical industry. He replaces outgoing Chairman and current Novartis CEO Vas Narasimhan, M.D. Pfizer CEO Albert Bourla, Ph.D., has been named chair-elect, and Sanofi CEO Paul Hudson will be the group’s new treasurer. 
PhRMA’s to-do list has grown in the last year beyond just countering the Inflation Reduction Act (IRA). It’s now fending off the threat of march-in rights from the Biden administration and has a slightly shrunken roster after the departures of AbbVie, AstraZeneca and Teva. Earlier this month, PhRMA’s lawsuit against the IRA was dismissed because it “lacked subject matter jurisdiction,” according to the judge. A PhRMA spokesperson said then that the group was weighing its next steps. Fierce Pharma

Vir Biotechnology CMO steps down
Vir Biotechnology
Vir’s EVP and Chief Medical Officer Phil Pang, M.D., Ph.D., is leaving the biotech at the end of March, triggering a hunt for a successor.
Pang, who is stepping down to spend more time with his family, has been with the California-based company for more than seven years.
“I leave a very capable development team that will inform the strategy and enable a smooth transition for a new chief medical officer,” Pang said in a Feb. 20 release. 
Before joining Vir back in 2016, Pang held leadership roles at Riboscience and Gilead Sciences. Release

> After a 20-year run at the FDA, Stephen Grant, M.D., has left the federal agency to become chief regulatory officer at Saghmos Therapeutics. Previously, Grant served as the deputy director for the FDA’s division of cardiology and nephrology. Release
> Almost a year after stepping down as head of Bausch + Lomb, Joseph Papa is taking the reins at Emergent BioSolutions. Papa succeeds Haywood Miller, who transitioned from an advisory role to become interim CEO in June 2023, when Emergent’s then-leader Robert Kramer retired. Fierce Pharma
> Former Eli Lilly VP Renee Williams departed the company at the end of 2023 and launched her own consulting firm based in the Bay Area. Before joining Lilly in 2022 she led business strategy and operations for Janssen’s (now Johnson & Johnson Innovative Medicine) infectious disease unit. 
> Ikena Oncology’s chief medical officer Sergio Santillana, M.D., has resigned, with Caroline Germa, M.D., taking his place. Germa joins from Transcenta Therapeutics, where she served as EVP of global medicine development and CMO, and previously held senior leadership roles at AstraZeneca, Bristol Myers Squibb and Novartis. Release
> Synthekine is shaking things up, selecting Geoff Nosrati, Ph.D., to serve as chief business officer; Martin Oft, M.D., as chief scientific officer; and Greg Yedinak to serve as chief technical officer. Before Synthekine, new CBO Nosrati held the same role at Nutcracker Therapeutics, while Oft was Synthekine’s previous chief development officer and Yedinak was Synthekine’s SVP of technical operations. Release
> James Burke, M.D., has departed newly public CG Oncology to become chief medical officer at KaliVir Immunotherapeutics. Burke has previously served as CMO for Sillajen, Jennerex and Turnstone Biologics. Release
> Bhaskar Sambasivan is Saama’s new CEO, taking the reins from Vivek Sharma, who is stepping down for personal reasons. Most recently, Sambasivan served as CitiusTech’s CEO and was chief strategy officer and president of patient services at Eversana before that. Release
> Cell therapy biotech Poltreg has picked Daniel Shelly, Ph.D., to serve as chief business development officer. Shelly joins from Prescient Therapeutics, where he was VP of business development and alliances. Release
> Women’s health company Harmonia Healthcare has unveiled itself. The company is led by co-founder and president Leslie Gautam alongside Chief Scientific Officer and 2024 Time Women of the Year honoree Marlena Fejzo, Ph.D. Release 

Frontier CEO weathers 'one of the hardest financings' of his career to close $80M series C

Frontier Medicines has just closed a $80 million fundraising, but, according to CEO Chris Varma, Ph.D., corralling the capital was, in his own words, harder than the bleakest days of the Great Recession. 
“I’ve been either an investor or an entrepreneur [and] CEO for a long time—well over two decades—and this is definitely one of the hardest financings I’ve ever done,” he said in an interview. “I actually think that fundraising last year was worse than the fundraisings I’ve done during the eye of the financial crisis, even dating back to the dot com bubble bust.”

He attributed the difficulty in part to the tech sector beginning its recovery last year, drawing in early-stage investors, while drug developers scratched and clawed for new money. 

To make Varma’s job harder, he had to sell investors on why Frontier and its lead dual-inhibiting KRAS G12C asset were different from its competitors. Mainly, that meant Mirati Therapeutics, which presented some hard lessons for Frontier as the company rebounded from the European rejection of its KRAS cancer med Krazati. Mirati requested a reexamination that was ultimately successful to secure a positive opinion. All this happened at the same time that Bristol Myers Squibb worked to close its acquisition of Mirati. 

“What we’ve learned from that is you’ve got to develop a molecule that can address—for KRAS specifically—the on and the off forms at the same time [and] completely knock out the mutant target so that you can see transformative benefit for patients,” Varma said. 

KRAS lives in both an “on” and “off” state depending on which other guanine nucleotide-binding proteins (G-proteins) it’s bound to, impacting how it transmits upstream signals. Frontier’s lead asset, FMC-376, is a small molecule for both states, which is expected to maximize inhibition and wipe out the mutant forms of the gene altogether.
In conjunction with the financing, Frontier has dosed the first patient in a phase 1/2 trial testing FMC-376 in patients with solid tumors. The new money will go toward advancing that trial and other follow-up candidates. 
With investors like Deerfield and RA Capital backing the company through its previous two raises (RA joined the series B syndicate), Frontier considered an IPO this time around, Varma said, deciding ultimately that because they don’t have to, they probably shouldn’t. He also said it helps to have clinical data in hand when you hit Wall Street, something he expects by the end of this year, teeing up a potential IPO afterward. Joining the investor team is Galapagos, the Dutch biotech that in addition to an approved JAK1 inhibitor is developing two cell therapies aimed at cancer and autoimmune diseases. 
On the surface, Frontier seems like the kind of biotech that could have scared off investors because of the possible Inflation Reduction Act implications. It’s a small-molecule-focused startup with a lead asset looking to topple existing entrants in the space. To Varma’s surprise, the topic didn’t come up as much as he thought it would in fundraising talks. Aiding Frontier’s case, Varma thinks, is that the company’s platform is disease-agnostic, though early undisclosed candidates are largely aimed at cancer.

“From the very beginning, we have been looking at disease targets in cancer and immunology and other areas,” he said. “We’re going to broaden our therapeutic focus over time.” 

'Golden era of innovation': ORI Capital raises $260M fund for early-stage biotechs

ORI Capital has raised $260 million, the venture capital firm’s second life sciences fund that will go toward early-stage biotechs worldwide.
The Hong Kong- and U.S.-based investment firm will support companies focused on diagnostics, therapeutics and drug delivery for conditions with large unmet need and high mortality rates, according to a Feb. 22 release. Those indications include cancer, metabolic disorders and neurodegenerative diseases, ORI said.

The VC touts an AI-driven research platform and has identified themes such as next-gen small molecules, programmable nuclear acid therapies, immuno-oncology cell therapy and synthetic biology as key drivers of growth. The company’s new fund will be used to invest in companies pursuing these approaches.

“We are in a golden era of innovation across the intersection of AI and biology, where technological breakthroughs are creating new approaches to diagnosing and treating disease,” Simone Song, founding partner of ORI Capital, said in the release. “We believe the current environment provides an attractive opportunity for investing in the next generation of leading biotech companies.”   

Since launching in 2015, the VC has supported several companies with notable exits, including CG Oncology’s recent IPO that raised an upsized $380 million.

Investors hone in on Moderna’s RSV, CMV prospects after ‘transition’ year

After 2023 COVID sales landed at the low end of Moderna’s estimates, company executives and investors alike are turning their attention towards tantalizing late-stage programs, namely respiratory syncytial virus (RSV) and cytomegalovirus (CMV).
That was the vibe on the Flagship breadwinner’s fourth-quarter earnings call Thursday, with the company slated to hear back from the FDA on its RSV vaccine by the middle of May. This year is also expected to mark the first tranche of efficacy data on Moderna’s CMV vaccine, though the timing is contingent on case accrual. 

President and head of R&D Stephen Hoge, M.D., explained on the call that the first interim analysis will be triggered once 81 cases of infection have been accrued. If the study hasn’t reached statistical power at the first analysis, then it will carry on until a final analysis, marked by 112 cases. Based on the current pace, Hoge expects the study “will have more than enough cases this year.” 

“We are therefore pretty confident that we’re going to be seeing a readout from the interim analysis, possibly even a final analysis for efficacy in 2024,” he said. But since these readouts are event-driven, he cautioned that “we just have to bide our time.” 

As for Moderna’s RSV prospect, Hoge said that he and the team continue to feel “really enthusiastic” about the data and described the vaccine’s durability as “quite encouraging.” Earlier this month, Moderna reported that MRNA-1345 had an overall efficacy of 63.3% in patients 60 years and older with a median follow-up of 8.6 months, down from 84% efficacy at the 3.3-month mark. GSK’s Arexvy had a 67.2% efficacy over two seasons, while the efficacy of Pfizer’s Abrysvo fell from 66.7% to 49% across the two seasons. 

Hoge said he does not expect CDC advisers to have different administration recommendations for the three vaccines, should Moderna’s be approved at the agency’s June meeting.
“We would suspect that they will continue to view the products as more similar than not and therefore continue with consistent recommendations,” he said.
The potential for a new marketable vaccine along with late-stage CMV data and investors’ excitement around Moderna’s Merck-partnered melanoma treatment may have been behind the almost 9% rise in the company’s share price, from $87.59 to $95.26 by 10.40 am ET on Thursday.
It’s a positive start to the year after dwindling COVID sales diminished the stock price by more than $60 per share over the course of 2023. Moderna CEO Stéphane Bancel described 2023 as a “year of transition” in the latest earnings announcement. 

AbbVie wraps up $64M oncology, immunology deal with Tentarix

AbbVie is wrapping its tentacles around a few more oncology and immunology candidates thanks to a new $64 million deal with Tentarix Biotherapeutics.
The announcement was low on detail, but the two have inked a multiyear collaboration to discover and develop biologics in the two disease areas using the biotech’s Tentacles platform. The company’s tech designs biologics that activate immune cells to modulate disease pathways while avoiding safety concerns typically associated with less specific immune cell targeting.

Tentarix will receive $64 million in upfront option payments for two programs under the deal, according to a Thursday release. In return, AbbVie scores an exclusive option to acquire the programs after candidate nomination for an undisclosed payment.

This seems to be the deal sweet spot for Tentarix, which signed a similarly sized and frankly, nearly identical, partnership with Gilead Sciences in August 2023. The two companies agreed to work on therapies for oncology and inflammatory diseases, with $66 million upfront paid by Gilead.
Tentarix conducted a $35 million series B financing in September 2023 to raise funds for the Tentacles platform. Gilead participated in the raise, which was led by Amplitude Ventures with founding investors Versant Ventures and Samsara BioCapital also pitching in.

The raise brought Tentarix’s total capital raise to $132 million including upfront partnership payments at that time.
AbbVie, meanwhile, is in a period of great change, as long-time CEO Richard Gonzalez prepares to pass the helm over to President and Chief Operating Officer Robert Michael. The incoming chief executive will be in charge of charting a course post-Humira, after the patent expired on that megablockbuster. 

Bavarian Nordic ends cancer vaccine program to fully focus on profitable infectious disease range

Bavarian Nordic may be celebrating its most profitable year yet on the back of mpox vaccine sales, but that hasn’t stopped the Danish biotech from streamlining its portfolio.
The vaccine company’s immuno-oncology project, dubbed TAEK-VAC, was undergoing a phase 1 trial in patients with advanced HER2 and brachyury-expressing cancers. But Bavarian said the program has now “reached a stage where clinical expansion and further investments would be required.”

“The company has decided to focus its future R&D efforts on infectious diseases through product improvements to remain competitive and new vaccine development,” the company explained in a full-year 2023 financial report Wednesday. “As a consequence, the TAEK-VAC project will not be continued, and the company has no further plans to invest in immuno-oncology vaccine development.”

TAEK-VAC was a tumor antibody enhanced therapeutic vaccine that used Bavarian’s MVA-BN platform. While therapeutic cancer vaccines are in the works at the likes of mRNA mainstay Moderna and Ultimovacs, Bavarian Nordic is now focused on more immediately lucrative options.

The Copenhagen-based biotech’s preliminary 2023 results “represent the best-ever financial result in the company’s history,” the company said. This jump was driven by “extraordinary growth” in its travel health range as well as a “surge” in sales of the dual smallpox/mpox vaccine Jynneos.

Bavarian’s approved travel health portfolio spans tick-borne encephalitis vaccine Encepur, GSK’s rabies vaccine Rabavert, cholera vaccine Vaxchora and typhoid vaccine Vivotif.
These combined to produce 2023 preliminary revenue of 7.06 billion Danish kroner ($1.02 billion), more than double the company’s 3.15 billion kroner ($460 million) haul for 2022 and overshooting Bavarian’s 6.9 billion ($1 billion) guidance for last year.
“This historical result is an endorsement of the successful execution of the commercial strategy we initiated back in 2020 and the transition to one of the largest pure play vaccine companies in the world,” CEO Paul Chaplin said in the release.
“While the surge in demand for our smallpox/mpox vaccine is decreasing, in part due to the role our vaccine has played in reducing the mpox cases, the public preparedness base business has grown in the number of customers and the emerging private mpox business,” Chaplin added.

The company already shelved plans for a COVID-19 vaccine in September 2023 after phase 3 data showed the candidate struggled against newer variants of the virus. The decision came just months after Bavarian dropped a respiratory syncytial virus (RSV) vaccine over a late-stage failure.

As FDA takes up Dato-Dxd, AstraZeneca's David Fredrickson places next ADC bet on in-house pipeline

When he sat down with Fierce Biotech back in August 2022, David Fredrickson made no secret of the fact that AstraZeneca’s antibody-drug conjugates (ADCs) excited him most about the Big Pharma’s oncology pipeline.
Since then, ADCs have become the hottest ticket in town for biopharma dealmaking, with everyone from GSK to Eli Lilly and Bristol Myers Squibb fronting serious cash to pad out their own pipelines. As ADC fever spreads across the sector, Fredrickson’s own passion for the modality remains undimmed today.

“I remain incredibly enthusiastic that antibody-drug conjugates have the potential to replace classical chemotherapy across so many of the settings where today we see chemotherapies being utilized,” the executive vice president of AstraZeneca’s oncology business unit said in an interview Tuesday.

Fredrickson spoke to Fierce Biotech the week that the FDA accepted an application for the company’s TROP2-directed ADC datopotamab deruxtecan, or Dato-DXd for short. Like AstraZeneca’s blockbuster Enhertu, Dato-DXd is a collaboration with Japan’s Daiichi Sankyo, and the drug is currently being considered by the FDA as a treatment for non-squamous non-small cell lung cancer (NSCLC).
The agency expects to give its verdict Dec. 20, according to Daiichi (PDF). An approval application in HR-positive, HER2-negative breast cancer has also been submitted to the FDA.

The lung cancer submission is based on data from the phase 3 TROPION-Lung01 trial, which showed that median progression-free survival (PFS)—one of the study’s primary endpoints—was 5.6 months in patients treated with Dato-DXd versus 3.7 months among those treated with the chemotherapy docetaxel.
The trial also assessed Dato-DXd in patients with squamous NSCLC, but it didn’t demonstrate a PFS benefit in this group, resulting in the more limited non-squamous indication application that the FDA accepted this week.

David Fredrickson, executive vice president of AstraZeneca’s oncology business unit
(AstraZeneca)

There are still more data to come. While the trial has so far shown a “numerically favorable” trend for overall survival—the study’s other primary endpoint—AstraZeneca is waiting for a final analysis.

“Final overall survival data for TROPION-Lung01 will become available during the review period,” Fredrickson explained. “Maintaining the trend that we’ve seen so far would certainly be very positive. If it goes the other way, then that would be a separate review discussion that we’d have with the agency, obviously.”
The trial data have raised other issues, most notably an undetermined number of deaths attributed to interstitial lung disease that AstraZeneca and Daiichi discussed at last year’s European Society for Medical Oncology (ESMO) Congress.
Fredrickson accepts that the FDA will be taking these adverse events into account as part of its decision-making process, but he’s confident in the solution the companies set out at that conference.
“Interstitial lung disease is certainly a serious adverse event and one that needs to be well understood,” he said. “We were able to characterize and understand it in a way that we think allows for the awareness and monitoring programs that we’ve been working on for Enhertu to also be similarly applied to this program.”

With more data to come and a narrower initial regulatory focus, it’s perhaps unsurprising that Fredrickson doesn’t want to be drawn on whether AstraZeneca expects Dato-DXd to have the same blockbuster sales potential as its hugely successful sibling Enhertu.
“I believe that Dato has the potential to be very transformative, particularly in the treatment of lung cancer,” he said. “The data sets that we saw at ESMO of last year and that the filing has been based upon are what gives me that belief.”
“So we’re optimistic that we’re moving in the right direction, but we also recognize that there’ll still be more data that’s going to be coming along the way,” he added.
Should the FDA’s December decision go AstraZeneca’s way, there’s a potentially lucrative prize to be had. The recent failure of Gilead Sciences’ Trodelvy to show a statistically significant overall survival benefit compared with chemo in a phase 3 lung cancer trial means Dato-DXd has a chance to become the first TROP2-targeted ADC to reach NSCLC.
AstraZeneca isn’t the only Big Pharma that’s now working with Daiichi in the ADC space, either. Coming up behind Dato-DXd are three other ADCs that the Japanese drugmaker has been working on, and for which Merck & Co. paid $4 billion upfront in October to co-develop.

Fredrickson gave no clue as to whether AstraZeneca also put in a bid for those assets, instead pointing to his company’s rapidly progressing stable of in-house ADCs. The Big Pharma already has four of its own candidates in phase 1/2 development, including the B7-H4-targeting AZD8205, which is in a midstage study for solid tumors, and a bispecific ADC dubbed AZD9592.
There’s also AZD0901, a Claudin18.2-specific antibody bought from KYM Biosciences last year that’s now in a phase 2 trial for solid tumors.
“We’re making sure that we have what we think is the most robust portfolio of antibody-drug conjugates,” Fredrickson said. “We think that Enhertu and Dato are two of the obvious leaders, but we have our own wholly owned antibody-drug conjugates that we think have compelling payload-linker combinations and also compelling targets that are going to complement the work that we’re doing in lung cancer, breast cancer, GI cancers and gynecologic malignancies—areas that we have strong leadership positions.”
“Enhertu, Dato and our wholly owned ADCs represent for us where we want to be placing our bets for the future of this class,” Fredrickson added.

RAPT faces 'unfortunate and unexpected' clinical hold after liver failure in atopic dermatitis trial

Rapt Therapeutics is reeling from an “unfortunate and unexpected” clinical hold after a patient in a phase 2 immunology trial experienced liver failure that may be related to the study drug. 
That’s how CEO Brian Wong, M.D., Ph.D., described the turn of events in Tuesday’s press release, adding that Rapt is working to learn more about what happened: “Patient safety is our top priority and we will work with the FDA to resolve this as quickly as possible.”

The serious adverse event occurred in a phase 2b atopic dermatitis trial. The cause remains unknown but Rapt said the event may be “potentially related to zelnecirnon.”

The FDA notified Rapt of the clinical hold on both the phase 2b atopic dermatitis trial and a phase 2a study in asthma. 
Rapt noted that roughly 350 patients have been treated with the drug across three trials and no signs of liver toxicity had been reported before now and there has been no evidence of potential liver toxicity in clinical trials. At the end of November, Rapt published phase 1 data of zelnecirnon which found that the drug was “generally well-tolerated” with no serious adverse events and that all reported side effects were mild-to-moderate. 

Rapt implied that there may be more variables at play with the individual patient beyond just receiving the study drug. The South San Francisco biotech says that the person had a drug allergy to Dupixent, an autoimmune disease requiring thyroid hormone replacement therapy, contracted COVID-19 during the trial and used “an herbal supplement known to be associated with liver failure.” 
That meant little to investors, with the company’s share price nosediving after the markets opened Tuesday, down 64% from $25.97 to $9.25.
Rapt is supposedly just a few months away from reporting interim data, saying in a third-quarter earnings report that initial atopic dermatitis data was expected by the middle of the year. 
With the inflammation program on hold for now, all attention turns to Rapt’s phase 2 oncology med, tivumecirnon, which is being tested alone and in a combo with Merck & Co.’s Keytruda.

Rapt reported $184.8 million in cash on hand at the end of September, enough to last into the middle of 2025.