Last Week Tonight in BioPharma: April 4th - April 10th
A no-go for Replimune, faster INDs, and mid-cap biotechs writing checks
We’re back for the third edition of Last Week Tonight in BioPharma (LWTB)!
In case you’re new, here is what I am trying to do with this series:
A short recap of the most interesting stories from the past week with strategic insights to get you ready for your Monday meetings.
Up to 3 key events per category:
Press Release Decoder: going beyond the company speak, reading between the lines, thinking about what isn’t being said, to illustrate the strategic implications of a company’s moves that don’t make it into the press release
Connecting the Dots: looking at stories that are either about the macro or from the mainstream news and how they may impact BioPharma
Follow the Money: quick takes on some key deals that were struck and what they mean for those companies, their competitors, or the sector at-large
Free to all subscriber levels! Although if you like my free content and have $8/month to spare (or expense to your company), I think you’ll love the deeper analyses my paid subscribers get. You can upgrade at any time by clicking the button below.
And with that, let’s get into what happened this past week.
📡 PRESS RELEASE DECODER
What the press releases actually mean
Replimune's RP1 Receives a Second FDA Complete Response Letter — And This Time, It Looks Terminal
Source: FDA / Replimune IR | Date: April 10, 2026
The FDA issued a second CRL for Replimune's BLA for RP1 (vusolimogene oderparepvec) in combination with nivolumab for adult patients with advanced melanoma who progressed on anti-PD-1 therapy. The new CRL was reviewed by an entirely different clinical review team than the first — assembled specifically to "maintain objectivity" — and that team unanimously concluded the data are insufficient to demonstrate substantial evidence of effectiveness. The FDA cited inability to isolate RP1's contribution when combined with nivolumab, heterogeneity of the IGNYTE trial population, unreliable response assessments (including the finding that 53% of responders had no non-injected target lesions to assess systemic activity), and the inadequacy of the resubmission package, which included an unplanned interim look at just 40 patients from the ongoing Phase 3 RP1-104 trial (10% of planned enrollment). Replimune's press release struck a combative tone, accusing the FDA of "inconsistent communication and a fragmented and slow-moving regulatory process," announcing substantial layoffs and the scaling back of US manufacturing operations, and stating that "without timely accelerated approval, the development of RP1 will not be viable."
BPS’ Take: I spent a lot of time reading the actual CRL and Replimune’s response side by side, and this situation is genuinely more complicated than either side is letting on. Kenny and I discussed the Replimune situation in detail during an old podcast episode (link). My take then was that this FDA was pulling the rug out from under them and unfairly blocking an important new medicine from being available to late-stage melanoma patients. Now I’m not so sure who is right, but I am very certain both the FDA and Replimune are obscuring the truth, which is a bad look for all parties involved.
The FDA’s scientific case on response assessment integrity is strong. When over half of your responders had all their target lesions injected with the virus that’s a fundamental interpretability problem. Add the confounding from surgical excisions of target lesions before response assessments and re-injection of enlarging tumors before independent review could call progression, and the reported 33% ORR may be artificially inflated. Replimune did a sub-par job maintaining high standards of data quality when running their study. That to me seems pretty clear.
But Replimune’s process complaints also have teeth. They claim a senior member of the original review team publicly stated that the clinical team believed the data supported contribution of effect, but leadership disagreed. If that’s true, assembling a “new” review team to ensure “objectivity” looks less like good regulatory practice and more like opinion shopping. Replimune also claims the FDA acknowledged at the September 2025 Type A meeting that randomizing patients to anti-PD-1 alone was not feasible and didn’t raise further heterogeneity concerns after melanoma expert testimony, only to resurrect both issues in this CRL. And they say they submitted data based on an FDA suggestion, asked for feedback, received none, had the resubmission accepted as a “complete response,” and then got rejected on the very approach they were told to pursue. Add to all this that the drug received breakthrough therapy designation, but also in 2021 the FDA said they recommended a control arm, and it makes for a really confusing story.
The contribution-of-effect argument is where I have the most sympathy for Replimune. Every one of these patients had already failed anti-PD-1 therapy. The expected response rate to nivolumab re-challenge in this population is about 6-7%. IGNYTE showed ~33%. You don’t need a randomized control to know nivolumab alone isn’t generating that response. The “failed A, now give A+B” paradigm is well-established in oncology. I think it would be different story if the FDA requested an RP-1 monotherapy arm, but that doesn’t really seem to be the case.
Where does this leave things? Replimune is essentially signaling that the program (and perhaps their company) is dead. This is a bad outcome for melanoma patients who have limited options after PD-1 failure, perhaps at least one nail in the oncolytic virus field (at least for a little bit), a cautionary tale about the risks of pursuing accelerated approval on a single-arm combination study without a concurrent control, and a warning not to make enemies with the FDA. Industry and regulators need to work collaboratively. That’s how new drugs have the best chance of getting approved even when evidence is imperfect.
Lessons for me? I think despite the improvement this FDA has made in CRL transparency, we the public, still aren’t getting a full enough story to adjudicate blame when these situations arise. I could have done a better job considering the posibility that Replimune managed their study poorly, which played into the CRLs.
🌐 CONNECTING THE DOTS
When the outside world meets biopharma
Ben Sasse, Pancreatic Cancer, and the Harsh Reality of Novel Cancer Treatment
Source: New York Times Opinion | Date: April 9, 2026
The New York Times published a profile of former Nebraska Senator Ben Sasse, who announced in December 2025 that he has Stage 4 metastatic pancreatic cancer. The piece — an edited transcript of an interview on the "Interesting Times" podcast — chronicles Sasse's reflections on mortality, family, faith, and living with a disease he bluntly called "a death sentence." Sasse is 53 years old. In the interview he reveals he is taking daraxonrisib, Revolution Medicine’s pan-RAS(ON) inhibitor that was the reason for many buyout rumors a few months back. Sasse also bares openly a bloody face in the interview, a result of the drugs on-target AE profile.
BPS’ Take: Pancreatic cancer has a five-year relative survival rate of 13%. For Stage 4 disease specifically, it drops into the single digits. Luckily daraxonrasib has shown promising signals in this setting, where many past drugs have failed. It’s probably not going to cure Sasse, but it is a tremendous step up in life extension compared to the slew of chemo and radiation that is standard of care. The interview is also a great reminder of how much patients can still suffer despite their cancers shrinking. Bleeding from the face, nausea, dependency on morphine - all of that adds to the physical tole of fighting cancer and is a reminder of how much further we still have left to go in conquering this family of diseases.
FDA Proposes Clinical Trial Notification Pathway — Makary’s Biggest Structural Reform Yet
Source: FDA FY2027 Budget Proposal / BioSpace / RAPS | Date: April 3-8, 2026
The FDA, as part of its FY2027 budget proposal released the week of April 3, included a legislative request to create a new “Clinical Trial Notification Pathway” as an alternative to the existing Investigational New Drug (IND) application process. The current IND system requires sponsors to compile extensive toxicology, pharmacology, and manufacturing data before initiating first-in-human trials, triggering a mandatory 30-day FDA review hold. The proposed new pathway would create an expedited alternative for Phase 1 programs where adequate preclinical data already exists, modeled in part on Australia’s Clinical Trial Notification system that delegates scientific and ethical review to local committees rather than requiring national regulator sign-off before trials begin. FDA Commissioner Marty Makary framed the proposal as part of the agency’s transition “from a reactionary system to a proactive system,” citing concerns that the current regulatory burden is driving early-stage clinical trials overseas — particularly to China, which has been attracting early-phase research through its own decentralized trial system and lower labor costs.
BPS’ Take: This is potentially the most consequential structural reform Makary has proposed since taking over the FDA. More than releasing the CRLs and more than the 2-month PRV. If implemented, a Clinical Trial Notification pathway would fundamentally change the speed and economics of Phase 1 development in the US.
The Australia comparison is apt. The Australian CTN system is a major reason why companies like to run early-phase work down under. You can get into clinic weeks faster and get clinical proof-of-concept that much sooner. Makary is essentially arguing that if we don’t create a competitive alternative here, the US will keep hemorrhaging early-stage trial activity to jurisdictions with faster regulatory onramps (notably China). Chinese clinical trial volume, especially for testing novel drugs in Phase 1, has exceeded the US by some measures. This is driven in part by cost advantages but also a more streamlined early-phase regulatory process.
This change would be a big boost to the entire AI for Drug Development field too, as it would speed up the rate it which novel biology could be tested in humans, speeding up the data (and increasing the quality of data) that could feed into AI platforms.
Where this may get hung up is that it requires Congressional legislation. That means it has to survive the appropriations process, potential industry lobbying (some large pharma companies could benefit from the IND burden because it raises barriers to entry for competitors), and whatever political dynamics are at play by the time this hits the floor. Hopefully the anti-China competitive argument is sufficient enough to push this through, as it would benefit innovation significantly over the long run.
💰 FOLLOW THE MONEY
Deals, dollars, and what they signal
Gilead Acquires Tubulis for Up to $5B — ADC Platform Play Gets Aggressive
Source: Gilead Sciences Press Release / Reuters / STAT News | Date: April 7, 2026
Gilead Sciences announced a definitive agreement to acquire Tubulis GmbH, a Munich-based clinical-stage ADC company, for $3.15 billion upfront in cash plus up to $1.85 billion in contingent milestone payments. Tubulis’ lead asset is TUB-040, a NaPi2b-directed topoisomerase-I inhibitor ADC currently in Phase 1b/2 for platinum-resistant ovarian cancer and non-small cell lung cancer. The company also brings TUB-030, a 5T4-targeted ADC with early clinical data in solid tumors, and a proprietary conjugation platform featuring its Tubutecan linker-payload technology designed to improve ADC therapeutic index. The deal follows a two-year collaboration between the companies and builds on Gilead’s oncology transformation through prior acquisitions of Immunomedics (Trodelvy) and Kite (cell therapy). Tubulis will operate as a dedicated ADC research organization within Gilead, with Munich serving as a hub for ADC innovation. The transaction is expected to close Q2 2026.
BPS’ Take: Gilead is buying time and technology simultaneously. Trodelvy faces growing competition from the AstraZeneca/Daiichi Sankyo Enhertu partnership and a wave of next-gen ADCs. Tubulis’ conjugation technology — specifically the Tubutecan linker-payload system — is the kind of platform asset that could generate compounding value. Its lead asset is focused on Napi2b, a once failed target (i.e Mersana), but the dollar signs associated with this deal signal that this ADC format may be meaningfully differentiated than its predecessors. With the $3.15B upfront for a company with one asset in Phase 1b/2, but a differentiated platform behind it, Gilead is signaling that they both believe in Tubulis’ lead compound and are ready to discover and develop their own ADCs moving forward. AstraZeneca proved that owning an ADC platform (via the Daiichi Sankyo partnership) creates compounding value across tumor types and Gilead is trying to do the same. However, sometimes you buy things thinking they are a platform company and they just turn out to be a pipeline-in-a-product company. We’ll see where this one ends up.
I found it interesting that Gilead felt the need to host a call to discuss this acquisition as well as the previous Arcellx and Ouros deals all in one, as all these deals were relatively spread out in time and not all that huge (by Gilead standards). In any case, you are seeing a clear coloring-in of the lines for what programs Gilead envisions carrying its revenues into the future, outside of its HIV powerhouse. They are going to be anchored in Cell Therapy for heme/onc, ADCs for solid tumors, and B-cell depletion for auto-immune disease, with optionality on other modalities coming from existing partnerships.
Neurocrine Acquires Soleno Therapeutics for $2.9B — A Rare Disease Bet With an EMA-Shaped Asterisk
Source: Neurocrine IR / Soleno IR / STAT News / BioPharma Dive / Reuters | Date: April 6-7, 2026
Neurocrine Biosciences announced the acquisition of Soleno Therapeutics for $53.00 per share in cash, approximately $2.9 billion total, to gain control of Vykat XR (diazoxide choline controlled-release) — the first and only FDA-approved treatment for hyperphagia in Prader-Willi syndrome (PWS). Vykat XR received FDA approval in March 2025 and launched commercially in Q2 2025, generating $190 million in early sales. PWS is a severe rare genetic disorder affecting approximately 400,000 patients globally and an estimated 20,000-30,000 in the US. The deal announcement on April 6 was followed the next day by Reuters reporting that Neurocrine and Soleno had jointly withdrawn the EMA marketing authorization application for Vykat XR in Europe, citing a request for additional data from European regulators. An EMA decision had originally been expected in mid-2026.
BPS’ Take: It’s rare to see smaller mid-size biotech do late-stage acquisitions like this, but I think more of these are healthy for the sector. It can’t just be the Big Pharmas doing all the acquisitions. We’ve seen the “middleweight” to “welterweight” class start do more deals as of late. Biogen last week, GenMab acquiring Merus, Biomarin acquiring Amicus, and Servier acquiring Day One. These are all commercial stage companies who are now operating like mini-Big Pharmas, using their cash flows to acquire late stage assets that boost their future inline revenues. Very interesting!
Vykat XR is the only game in town in Prader-Willi syndrome and has had a strong first months of launch. Competitor drugs, like that from Aardvark, have seemingly stalled, so their is clear runway here for Vykat XR to establish a meaningful commercial lead. The sales trajectory suggests there is a lot more upside to be had and the drug fits nicely into Neurocrine’s rare disease commercial infrastructure (Ingrezza in tardive dyskinesia, Crenessity in congenital adrenal hyperplasia).
The EMA market application withdrawal is a bit odd, especially when Europe is a major market. The deal math works if Vykat XR establishes itself as the undisputed standard of care for PWS hyperphagia in the US, but the European situation is a material overhang. I’d want to understand the specific nature of the EMA’s data request before calling this a clean win. Does Neurocrine think its better to punt on Europe entirely or is there more to the story?
Back next week with another edition of LWTB! Stay tuned and hope you have a strong start to your week!