Medical Innovation Exchange

Biotechnology

Genentech axes Adaptimmune cell therapy deal as it presses ahead with staff cuts

In the same week that Genentech confirmed it’s cutting 3% of its staff, the Roche subsidiary has terminated a cell therapy partnership with Adaptimmune Therapeutics.
The collaboration, inked in 2021, was a licensing deal focused on the development of two types of allogeneic T-cell therapies: off-the-shelf therapies directed to up to five targets and personalized therapies using αβ T-cell receptors isolated from a patient, with these therapies being administered to the same patient.

At the time, Genentech paid out $150 million in cash and offered Adaptimmune the chance to earn $35 million in milestone payments. The deal termination will set in 180 days after notice of the decision was received, meaning the terms of the pact are effective until then, according to Securities and Exchange Commission filings.

Adaptimmune received word of the termination on Wednesday, according to the filing.
The Adaptimmune news comes shortly after Genentech confirmed to Fierce Biotech that it would be trimming roughly 3% of its workforce across “several departments.” Earlier this year, the biotech’s parent company Roche announced cuts to its product development team.
“Note that this limited reduction will allow us to shift resources to the areas that we believe can provide the greatest impact for patients,” a Genentech spokesperson told Fierce Biotech in an emailed statement. “We are actively hiring in a number of areas to bring forward our most promising molecules and capabilities, and we project that the overall workforce across Roche will remain stable throughout 2024.”

For Adaptimmune, the termination comes almost exactly one year after another pharma discontinued work with the biotech. In April 2023, GSK paid Adaptimmune $37.3 million to wipe its hands of two programs, one of which included lete-cel, an asset the company at one point touted as its leading cell therapy.
Then, in November, Adaptimmune axed two programs dubbed Gavo-cel and TC-510. After a review of safety and efficacy data for both candidates, the U.K. company said it didn’t “see a path forward” for further development of either programs.
Now, the company has zoomed in on launching afami-cel—which has snagged FDA priority review and is slated for an FDA decision by or on August 4 of this year—for patients with advanced synovial sarcoma.

“We’ve had a very valuable collaboration with our partner Genentech, and we continue to believe in the long-term potential of our iPSC-based allogeneic platform,” Adaptimmune CEO Adrian Rawcliffe said in an April 12 release. “Over the past 12 months, we’ve been resolutely focused on our late-stage autologous pipeline—in particular, our sarcoma franchise. We have the resources to deliver afami-cel to market as planned, and I look forward to updating on progress at our investor day next week.”

Portage Biotech hints at potential closure as it halts programs, hunts for strategic options

Portage Biotech is putting the clamps on existing work to save cash as it prioritizes a hunt for strategic alternatives. 
The company said Friday that after a review of the financing market and the amount of spending necessary to advance its pipeline, the search for strategic alternatives would commence. In the meantime, Portage is halting enrollment in a clinical trial testing both its adenosine 2A inhibitor PORT-6 and its adenosine 2B inhibitor PORT-7. Portage bought both assets from Tarus Therapeutics less than two years ago. 

Portage is considering anything from securing partners for its assets to a merger, sale or a full wind-down of the company. The biotech has no timetable for finding a path forward. 

About three months ago, Portage said it was all in on prioritizing development of its adenosine inhibitors, electing to pause further development of an iNKT program. The biotech had been expecting to provide interim data from a phase 1a trial testing PORT-6 in patients with solid tumors at this year’s American Society of Clinical Oncology annual meeting in June, with final data teased for November. 
But the company had little money to work with, entering 2024 with just $5.3 million in cash on hand, according to a full-year earnings report from February. Still, Portage affirmed at the time that it intended to press ahead with its adenosine work. 

Those assets were acquired from Tarus back in July 2022, with Portage handing over 2.4 million shares and taking on $3 million in liabilities. In addition to PORT-6 and PORT-7, Portage took hold of a dual adenosine inhibitor, PORT-8, and a preclinical candidate to treat gastrointestinal tumors, dubbed PORT-9. But neither PORT-8 or PORT-9 are still in development, according to Portage’s pipeline. 

Enlivex defends sepsis data that sank stock, shifting focus from mortality to subgroup analysis

Enlivex Therapeutics had a message Friday for investors who halved its share price: You’re misreading our data. The cell therapy developer blamed imbalances between cohorts for the mixed results—and contended the effect on a small subgroup of sepsis patients suggests the candidate has a future.
The phase 2 clinical trial compared Allocetra, an off-the-shelf cell therapy that is designed to reprogram macrophages, to placebo in the treatment of organ failure in adult sepsis patients. Enlivex takes cells from healthy donors and makes them express an “eat me” signal. After administration, macrophages duly eat the cells and homeostasis is restored. That’s the idea, anyway. 

Whether the phase 2 trial supports the efficacy of the mechanism is a point of disagreement between Enlivex and its investors. The biotech’s stock plummeted 54% to $1.83 in the wake of the release Thursday. Enlivex CEO Oren Hershkovitz, Ph.D., put his side across on a conference call with investors this morning. 

“Definitely we saw the market reaction, and we found that probably the market didn’t understand well the results, in our interpretation of the data,” Hershkovitz said. “This is a complicated study, and maybe people don’t read it the way we do. We’re pleased with the data and the results that we see. The market [reaction] is something that’s difficult to explain and understand for us. That came as a surprise.”

The case against Enlivex includes the mortality rate, which was 13.3% in the Allocetra arm compared to 2.2% in the control group. None of the deaths were deemed related to Allocetra. Enlivex noted that the mortality in both cohorts was lower than in historical studies and pointed to an imbalance between the control and treatment arms, which had a higher rate of septic shock and invasive ventilation at baseline.

Hershkovitz said the imbalance “made it challenging to deduce the relative effect” of Allocetra in the overall population. However, the CEO was willing to claim a “very good potential indication of effect” in a 15-patient subpopulation in which Allocetra appeared to have an advantage over placebo. The patients in the subpopulation had urinary tract infections.
Asked whether the results support plans to file for approval in Europe, Hershkovitz said Enlivex needs to collect more data. “Once we get all of the data and the interaction between the expression biomarkers and all that, we’ll probably consider to go and discuss that with the regulator,” Hershkovitz said.
The CEO later added he expects another trial will be needed “even if the results from all the other subgroups are good.”

Novartis may have bought MorphoSys, but it really only had eyes for BET inhibitor pelabresib: filing

Novartis may have emerged victorious from a bidding war for MorphoSys, but a peek into the deal negotiations reveals that the Swiss pharma would have been happier if it could have walked away with one specific asset.
Despite handing over 2.7 billion euros ($2.9 billion) cash to buy out the German biotech in February, the star of the show in Novartis’ eyes was always pelabresib, according to deal-related documents published yesterday. MorphoSys had been testing the BET inhibitor in combination with Incyte’s Jakafi in patients with myelofibrosis.

MorphoSys’ relationship with Novartis dates back decades and was strengthened in 2022 when the pharma paid $23 million in cash for the rights to the biotech’s preclinical cancer program. But as far as yesterday’s documents are concerned, the story really begins at the BIO International Convention in June 2023, when execs from both companies met up to discuss “potential strategic opportunities.”

The two companies did discuss pelabresib, although Novartis didn’t put any offer on the table at this stage. Over the following months, the Big Pharma made it increasingly clear it was interested in the drug, with those intentions becoming more concrete after MorphoSys published topline data from a phase 3 trial in November 2023 showing that pelabresib hit one primary endpoint on spleen volume reduction but missed another on significantly beating placebo on reducing symptoms.

By late December, Novartis was eyeing January’s J.P. Morgan Healthcare Conference as the best time to bring the companies’ respective CEOs together to discuss a deal. But when MorphoSys made it clear it already had another offer on the table, Novartis stressed that it would “move quickly” to stay in the game.

Novartis’ initial offer was sent on Jan. 3—to acquire all of MorphoSys’ shares for 55 euros ($58) apiece in cash. With a view to wrapping up the deal in two weeks, negotiations rolled ahead until Jan. 12, when Novartis threw a curveball—rather than buy the biotech outright, could the Big Pharma just pick up the pelabresib program via an acquisition of MorphoSys’ Constellation Pharmaceuticals unit?
To sweeten the proposal, Novartis said it might be willing to pay a higher price for pelabresib alone than if it came entangled with the rest of MorphoSys. But the biotech didn’t bite, and two days later Novartis had submitted an updated offer of 68 euros ($75) per share for the whole company. This would end up being the finalized offer, conditional on MorphoSys selling its sole commercial asset—lymphoma med Monjuvi—to longtime partner Incyte.
Novartis executives made no secret of the fact that pelabresib was the real prize when they went public with the deal in February. “We are excited about the opportunity of bringing pelabresib, a potential next-generation treatment combined with ruxolitinib, to people living with myelofibrosis, a rare and debilitating form of blood cancer,” the pharma’s chief medical officer Shreeram Aradhye, M.D., said at the time.

Chutes & Ladders—Top BIO lobbyist quickly exits after BIOSECURE reversal

 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. 

Top BIO lobbyist swiftly departs after BIOSECURE reversal 

Biotechnology Innovation Organization 
At one of the most consequential times for the biotech industry, the top lobbyist at the top trade organization is gone. Nick Shipley, BIO’s chief advocacy officer, left the organization last week, a spokesperson confirmed. He’s replaced by Aiken Hackett, BIO’s VP of federal government relations.  

Aiken Hackett
(BIO)

Shipley’s departure comes after BIO recently flip-flopped on its stance regarding the BIOSECURE Act, legislation filed in the U.S. House of Representatives that looks to clamp down on specific China-based contractors, namely WuXi AppTec, that are widely used by drug developers for manufacturing know-how. BIO was originally against the bill before siding with lawmakers. 
Shipley’s departure is also part of a wider reorganization, according to internal memos obtained by Stat. Evidently, new CEO John Crowley is shaking up the lobbying group a few months into his tenure after he started in December. Fierce Pharma 

Top Karuna leaders launch new venture after BMS buyout 

Seaport Therapeutics 
If there were any doubt that Boston’s Seaport district is a hotbed of new biopharma real estate, the launch of Seaport Therapeutics should seal the deal. 
The new biotech technically didn’t spin out of Karuna Therapeutics, but it may as well have. The company was co-founded by Steven Paul, M.D., Karuna’s chairman and former CEO who previously co-founded Sage Therapeutics and Voyager Therapeutics, and now-former PureTech Health CEO Daphne Zohar. PureTech helped assemble Seaport just as it did Karuna, with Zohar departing to be the new CEO of Seaport and Paul the inaugural board chair. 
The two are looking to build a second neuropsychiatric success story after Karuna was bought by Bristol Myers Squibb for $14 billion. The deal closed earlier this year with BMS expecting a decision from the FDA on Karuna’s lead schizophrenia drug in September. Fierce Biotech 

Orna snaps up top Kite exec as CMO 
Orna Therapeutics 
Circular RNA biotech Orna Therapeutics is hiring Frank Neumann, M.D., Ph.D., as its next chief medical officer, going to Gilead Sciences’ well to bolster its ranks.
Neumann joins from Gilead-owned Kite Pharma, where he was SVP and global head of clinical development. He’ll also join biotech venture capital firm MPM BioImpact, which launched Orna. Before joining Kite, Neumann was CMO at Verastem and head of oncology clinical research at bluebird bio. 
Orna’s lead asset is a discovery-stage anti-CD19 CAR. It has additional assets in the works in partnership with fellow MPM company ReNAgade Therapeutics. Release

> Nvelop, a gene editing startup founded in 2022 by genetic medicine luminaries David Liu, Ph.D., and Keith Joung, M.D., Ph.D., has emerged from stealth with $100 million in seed funding. The company is helmed by two former bluebird bio executives: CEO Jeff Walsh, who previously served as bluebird’s chief strategy officer; and Chief Scientific Officer Melissa Bonner, Ph.D., who served as bluebird’s SVP and head of research until joining Nvelop in September 2023. Fierce Biotech
> FundaMental Pharma has tapped Dirk Beher, Ph.D., to lead the neurodegenerative disease company, taking the CEO title from FundaMental co-founder Thomas Schulze, M.D. Beher is the former CEO and co-founder of CNS-focused Asceneuron and has past experience at Merck Sharp & Dohme, Amgen and Merck Serono. Release
> Preclinical biotech Nuevocor has named John Lee, M.D., Ph.D., as chief medical officer. Lee most recently held the same position at PhaseBio Pharmaceuticals and clocked in time at Quintiles and Bristol Myers Squibb before that. Release
> Chrystal Louis, M.D., is succeeding TScan Therapeutics’ Debora Barton, M.D., who has served as the company’s chief medical officer since July 2022 and is departing for personal reasons. Louis joins from Zentalis Pharmaceuticals, where she served as SVP of hematology clinical development, and has previously held roles at CRISPR Therapeutics, Bristol Myers Squibb, Celgene (acquired by BMS) and Merrimack Pharmaceuticals. Release
> Bayer subsidiary Asklepios BioPharmaceutical has appointed Mansuo Shannon, Ph.D., as the company’s new chief scientific officer. Shannon joins from Eli Lilly’s Prevail Therapeutics, where she also held the CSO title, and succeeds Asklepios co-founder R. Jude Samulski, Ph.D., who served as CSO since the company formed in 2001. Release 
> Eye care company Oculis has named Snehal Shah president of R&D. He joins from Iveric Bio, where he was chief regulatory and product strategy officer and led the team to an FDA approval of Izervay in an advanced form of age-related macular degeneration. Release
> Axplora CEO Sylke Hassel is stepping down, with Martin Meeson taking over the role. Meeson most recently helmed Fujifilm Diosynth Biotechnologies. Release
> G.ST Antivirals has chosen Ronald Bruce Turner, M.D., as the biotech’s lead asset enters a phase 2 rhinovirus study. Turner previously served as a professor of pediatric infectious diseases at the University of Virginia Medical School. Release 

Double autoimmune acquisitions as Century, Eliem each pick up peers

It’s been a busy morning for business development in the autoimmune space, with Century Therapeutics snapping up Clade Therapeutics and Eliem Therapeutics striking a deal for Tenet Medicines.
First up is Century, which is paying around $35 million upfront to acquire Clade and its αβ iT platform. Century’s President of R&D Hy Levitsky, M.D., said the platform has “delivered a process capable of exquisitely controlling iPSC differentiation toward definitive hematopoiesis and the generation of adaptive αβ CD4+ and CD8+ T cells for the treatment of cancer and autoimmune diseases.”

“Under the leadership of a pioneering team of scientists and senior leaders with decades of experience in stem cell biology and iPSC differentiation enabled by significant capital investment from their investors, Clade has established a discovery engine with industry-changing potential,” Levitsky added in an April 11 release.

Clade’s preclinical pipeline includes CLDE-308, an αβ iT cell program targeting CD19 in autoimmune disease and B-cell malignancies; CLDE-361, an αβ iT cell program targeting B-cell maturation antigen (BCMA) in the muscle condition myasthenia gravis; and an undisclosed iT cell focused research program in solid tumors.
Those three lead assets will “further enhance Century’s pipeline,” Levitsky said.
In return, Century is handing over $35 million in a mixture of cash and stock. There’s also a $10 million payment to play for upon achieving a specific clinical milestone.

Century announced the acquisition along with news that it had cemented a cash runway into 2026 courtesy of bringing in $60 million via a private placement of its common stock. Century’s lead program is a CD19-targeting allogeneic iNK cell therapy called CNTY-101, which is due to enter a phase 1 trial for severe systemic lupus erythematosus (SLE) later this year.
CNTY-101 rose to the front of Century’s pipeline in January, when the biotech de-prioritized investment in CNTY-103, a CD133-targeting CAR-iNK cell therapy candidate in preclinical development for glioblastoma, along with a discovery program for hematologic malignancies.
With the pipeline reprioritization, Century closed its lab operations in Seattle and Hamilton to consolidate its work in Philadelphia. Those moves meant a quarter of the company’s workforce was laid off.

Eliem tempted by Tenet’s lead asset
Meanwhile, the autoimmune disease potential of Tenet is what enticed Eliem to make its own acquisition this morning. Specifically, Eliem has its eyes on TNT119, an anti-CD19 antibody that has potential to treat everything from SLE to immune thrombocytopenia and membranous nephropathy.
Once Tenet has become absorbed by Eliem, TNT119 will become the merged company’s lead asset ahead of the candidate entering planned phase 2 trials for SLE and immune thrombocytopenia in the second half of the year. Tenet’s stockholders will own around 15% of the combined company.
Like Century, Eliem has also ensured its coffers are full as it goes into M&A mode. The company is bringing in $120 million via a private placement of its common stock that is due to close at the same time as the acquisition.
“The Eliem board of directors has conducted a thorough review of strategic alternatives, and we believe the transaction we are announcing today with Tenet presents a compelling opportunity for our stockholders,” Eliem’s executive chairman Andrew Levin said in an April 11 release. “We believe TNT119 represents a promising clinical asset across multiple autoimmune diseases targeting markets where there is a need for improved treatment options.”

The merger and the placement mean that the enlarged Eliem should have $210 million to hand in cash and equivalents. This will be enough to push TNT119 through its key upcoming milestones as well as fund the company’s operations into 2027.
Eliem has been searching for a savior since July 2023, when the biotech shuttered its last pipeline program and launched a search for strategic alternatives. Just a few months before, the nervous system disorder-focused company axed a phase-2-ready depression drug candidate and laid off 55% of staff, citing a “challenging capital environment” as the reason for ending work on its most advanced candidate.  

Novartis pays $150M for Arvinas' phase 3-ready prostate cancer protein degrader

Novartis is adding another weapon to its arsenal of oncology therapies, paying Arvinas $150 million upfront for rights to a phase 3-ready protein degrader that could treat a wide range of prostate cancer patients. 
The deal, which is worth up to $1.01 billion in milestones, will give Novartis global rights to ARV-766, a molecule designed to degrade wild-type and mutant androgen receptor (AR). Arvinas identified mutant degradation as a way to counter the drug resistance that can arise in patients taking AR inhibitors such as Astellas and Pfizer’s Xtandi and Johnson & Johnson’s Zytiga, but it now also sees earlier-line opportunities.

Novartis has signed up to explore the frontiers of ARV-766’s potential. The drugmaker, which is working to move its existing prostate cancer radiotherapy Pluvicto into earlier lines of therapy, has the R&D scale to tackle the opportunities that Arvinas now believes are open to ARV-766.

Arvinas indicated its interest in partnering the asset last year. Early-phase data convinced the biotech the addressable population for ARV-766 could be up to 120,000 patients with metastatic castration-sensitive and castration-resistant prostate cancer (CSPC/CRPC). 

As Arvinas CEO John Houston, Ph.D., told investors on a call to discuss ARV-766 in October, CSPC is “a much bigger enterprise in terms of trial size than CRPC and … that scenario clearly would lend itself to having a partner.” Houston added that “having a significant strategic partner for ‘766 as it moves to CSPC would be, I think, a relatively smart thing to do.”

The deal also includes the sale of Arvinas’ preclinical AR-V7 program. AR-V7 is an androgen receptor splice variant that some patients acquire. Preclinically, Arvinas’ first-generation AR asset bavdegalutamide did not degrade AR-V7.

Vertex pays $4.9 billion to hike Alpine’s immunology trail

Vertex Pharmaceuticals is buying Alpine Immune Sciences for $4.9 billion, the companies announced Wednesday afternoon. 
It’s the biggest acquisition so far this year, underscoring the immense investments that immunology and inflammation have drawn from biopharmas. Gilead’s $4.4 billion purchase of liver disease biotech CymaBay was the largest M&A deal before Thursday. And a week ago, Genmab made it’s largest-ever buy, scooping up cancer drug developer ProfoundBio. 

Vertex is set to get ahold of Alpine’s lead asset, povetacicept, a dual B cell cytokine agonist that Alpine says has best-in-class potential as a treatment for IgA nephropathy (IgAN).

New data from an open-label basket trial released Thursday found that povetacicept, given at 80mg once every four weeks, spurred a 64.1% reduction in proteinuria, an indicator of poor kidney filtration. Alpine plans to launch a phase 3 trial for patients with the indication in the second half of the year and is also testing the drug in patients with lupus and autoimmune cytopenias. 
Meanwhile, also in IgAN, Novartis is working on several assets, including Fabhalta and atrasentan, which the Swiss pharma obtained from its $3.2 billion acquisition o Chinook Therapeutics last year. Calliditas Therapeutics in December gained a full FDA approval for Tarpeyo, a formulation of budesonide, in IgAN.
The Alpine acquisition bolsters Vertex’s standing in the immunology space as other pharmas look to stand out. Johnson & Johnson CEO Joaquin Duato told investors in February that he sees opportunity for additional M&A in areas like neuroscience and immunology, and Takeda completed its $4 billion purchase of Nimubs’ TYK2 candidate back in February 2023. Other pharmas, like AbbVie, Bristol Myers Squibb and Sanofi, have doubled down on investing in immunology. 

Vertex CEO Reshma Kewalramani, M.D., said in a statement that she and the Vertex team look forward to exploring povetacicept’s potential as a “‘pipeline-in-a-product’”. 
Povetacicept’s profile has ascended within Alpine’s pipeline as delays and restructured agreements marked the recent history of AbbVie-partnered, acazicolcept. Alpine announced in late 2023 that the two had restructured their 2020 deal, with Alpine agreeing to stop the study early and accept a reduced option fee if AbbVie decided to opt into the asset. Alpine previously disclosed that phase 2 costs had exceeded expectations. 

Nearly a week after pulling Relyvrio, Amylyx to engage regulators about the drug's path in another rare disease

On the heels of Relyvrio’s market withdrawal in amyotrophic lateral sclerosis (ALS), Amylyx Pharmaceuticals has shared early data from a phase 2 trial in a separate rare disease that the biotech is touting as “clinically meaningful.”
The interim data come from an ongoing midstage trial, dubbed HELIOS, among adults with Wolfram syndrome, a rare genetic disease that impacts about 3,000 Americans. Patients with the autosomal recessive neurodegenerative condition have a poor prognosis, facing the possibility of severe neurological disability and premature death.

Amylyx believes AMX0035, a fixed-dose combination of sodium phenylbutyrate and taurursodiol, could slow neurodegeneration by targeting endoplasmic reticulum stress and mitochondrial dysfunction. The company is testing the investigational oral treatment among 12 patients in an open-label study measuring two primary endpoints: the drug’s efficacy and its safety and tolerability profile. 

The primary efficacy endpoint measures change from baseline in C-peptide, an established lab measure of pancreatic beta cell function and glycemic control. Early data from eight participants who have completed 24 weeks of treatment found average increases in total C-peptide responses at week 24.
For patients with Wolfram syndrome, a progressive decline would be expected on this measure without any treatment, Amylyx said in the April 10 release.

Meanwhile, AMX0035’s safety profile was consistent with earlier safety data and the drug was found to be generally well-tolerated, according to Amylyx. Most adverse events were mild or moderate, with no serious side effects related to AMX0035 treatment occurring.
The data demonstrated that AMX0035 had a “clinically meaningful effect” on key outcomes, such as the progression of diabetes, visual decline and overall disease burden, according to Amylyx. Figures regarding statistical significance were not shared.
When asked during a Q&A portion of an April 10 company call if the findings were statistically significant, Amylyx co-CEO Joshua Cohen said, “they are across many of the time points,” and later dubbed the findings as “statistically robust.”
“Outcomes for people with Wolfram syndrome consistently worsen over time, so disease stabilization alone is clinically meaningful for both patients and their doctors,” Fumihiko Urano, M.D., Ph.D., principal investigator of the HELIOS trial and professor at Washington University School of Medicine in St. Louis, said in the April 10 release. “The interim results from HELIOS that demonstrate improvement across multiple organ systems impacted by this progressive disease are encouraging.”

Investors didn’t appear to share the optimism. After the data were shared at market open April 10, the company’s share price fell by around 6% as of 3 p.m. ET.
Amylyx intends to meet with regulatory authorities to discuss a development path for AMX0035 in Wolfram syndrome, co-CEO Cohen said on the call. A topline data readout from HELIOS is slated for the second half of this year, he said.
In a February interview with Fierce Pharma, co-CEO Justin Klee said because Wolfram is an ultrarare disease, the company may pursue a different regulatory path than it did in ALS. HELIOS is the first interventional study in the indication, Klee noted.  

Back in 2020, the FDA granted AMX0035 orphan drug designation for Wolfram syndrome, a status given to certain investigational drugs that hold therapeutic potential in a rare disease.
The data drop comes less than a week after the company pulled AMX0035, approved as Relyvrio to treat ALS, from the market after the drug failed in a confirmatory trial. In the phase 3 study, Relyvrio didn’t beat placebo at improving patients’ physical function on the revised ALS functional rating scale, a key measurement of clinical benefit.
The failed trial and market withdrawal are serious setbacks in the ALS field, where there are few options to treat the fatal neurodegenerative disease.
Relyvrio had served as Amylyx’s sole source of revenue, so the withdrawal prompted the Massachusetts biotech to lay off about 70% of its workforce. The company employs around 100 staffers after the cuts. 
The biotech is also testing AMX0035 in a phase 3 trial in progressive supranuclear palsy, with a readout now expected around mid-2025.

AACR: To bring CAR-T to solid tumors, Poseida thinks we need to boost conditioning therapy

Why haven’t CAR-T therapies cracked into solid tumors yet? Poseida Therapeutics is trying to fill in at least one piece of the puzzle with a new analysis presented at the American Association for Cancer Research annual meeting showing that patients may need a higher dose of lymphodepletion than those with blood cancers.
The FDA has approved a handful of CAR-Ts in blood cancers such as Novartis’ Kymriah for lymphoma and leukemia and Gilead’s Yescarta for lymphoma. These therapies use engineered versions of patients’ own immune cells to recognize cancer antigens and fight the disease.

Many-a-biotech has popped up with bold promises of bringing the technology to solid tumors, too. But these therapies have run into myriad problems because they lack tumor-specific antigens and tend to wither in an immunosuppressive tumor microenvironment.

Poseida’s new retrospective analysis shows that patients with solid tumors might need a higher dose of conditioning chemotherapy to effectively prepare for allogeneic CAR-T treatment.

The company is hoping to add to the collective learning in CAR-T therapy, Rajesh Belani, M.D., told Fierce Biotech on the sidelines of the AACR meeting. Belani is vice president for clinical development at Poseida.

The assumption was that whatever worked for blood cancers would translate over to solid tumors, Belani said. But that doesn’t seem to be the case for the pre-conditioning regimen.
“Nobody has looked at this question,” Belani said.
Blood cancer patients typically receive a dose of 300 mg before starting CAR-T therapy. Poseida found that patients with solid tumors had higher white blood cell counts entering the trial and it wasn’t until the chemotherapy dose was upped to as high as 1,000 mg that they achieved comparable lymphodepletion.
With the higher conditioning dose, patients achieved better CAR-T cell expansion. In the AACR presentation, Poseida said “there was a trend” towards improved expansion of the biotech’s therapy, P-MUC1C-ALLO1, in those who received the 1,000 mg lymphodepletion dose.

Poseida also examined a 500 mg dose but found that the lymphodepletion wasn’t where it needed to be to proceed with CAR-T therapy.
Elsewhere at AACR, Poseida presented cohort data from a subset of patients in a phase 1/2 trial of P-BCMA-ALLO1, which is being developed with Roche in multiple myeloma.
The small dataset included five patients who had previously progressed after treatment with BCMA-targeted therapies such as bispecific T-cell engagers, antibody-drug conjugates (ADCs) or autologous CAR-T. These patients had received as many as seven prior treatments.
One patient’s response deepened to a “very good partial response” after receiving P-BCMA-ALLO1. The patient died about 60 days after therapy due to unrelated events, meaning the depth of response is hard to make sense of, analysts from William Blair noted in a Monday analysis.
Another patient also deepened to a very good partial response but progressed after 80 days. And a third patient has reached the same response that is continuing 120 days after receiving P-BCMA-ALLO1.
Enrollment in the phase 1/2 study will continue with patients who have prior BCMA exposure.