I managed to catch the Angelman's results webcast last night.
My take from the webcast, fwiw, is that Neuren is quite comfortable with the idea of forging ahead with one or two Phase 3 trials of NNZ-2591 and will continue to proceed in that direction. It’s not pure bluff. As Jon Pilcher has said, “there are completely different economics post-Phase 3”.
The Angelman indication, I suspect, may well not be advanced – this indication is third in line, the competitive landscape is different to PMS and PHS, Angelman comes under the FDA division of psychiatry whereas PMS and PHS come under neurology, and the Company estimates it has the resources to run just two Phase 3 trials by itself.
Jon Pilcher doesn’t believe that a larger pharma would get NNZ-2591 to market any faster. And while trial design, which obviously influences cost, still has to be agreed with the FDA (although by this stage Neuren will already have completed its proposed Phase 3 design), Jon is estimating each of the Phase 3 trials might cost somewhere between $50-100m. Of course, there’s also the other “various” undisclosed indications to consider which Jon has previously said won’t be announced until they are almost ready to commence Phase 2 trials.
In short, I don’t believe that it should be assumed that Neuren will be acquired either this year or next. That said, I do believe that Neuren is positioning itself for acquisition, I do believe that Neuren will be acquired and I do believe that it’s possible that takeover bids could emerge any time from Q4 this year onwards.
What I thought could be useful is to look at fairly recent large biotech acquisitions to get some sense of when the acquiring companies made their move and what was driving the acquisition. I’ve looked into the top 10 biopharma M&A deals of 2023, as listed by Fierce Pharma, and found, with the exception of Pfizer’s megadeal with Seagen, the transaction window was between a few months after Phase 2 results in the target company’s lead drug and up to a year following FDA approval of the lead drug. So, we would seem to be looking at a potential multi-year sweet spot and for Neuren, that sweet spot is about to begin.
The other thing I noted was that, in most cases, the lead drug was slted for multiple indications.
1.Pfizer and Seagen - US$43bn
Seagen was acquired for its proprietary antibody drug conjugate platform for cancer drugs and large pipeline of approved and clinical-stage drugs. Seagen had its first drug approved by the FDA approved in 2011. At the time of acquisition it had 4 FDA-approved therapies, additional clinical programs for those therapies and 11 other drugs in its pipeline.
Pfizer believed that its R&D, commercialization and manufacturing capabilities could accelerate the expansion of Seagen's portfolio. Pfizer had the capacity to run several large Phase 3 trials simultaneously, which the smaller company, Seagen, couldn’t achieve on its own.
2. Bristol Myers Squibb and Karuna Therapeutics - US$14bn
Karuna was acquired 1 month after the FDA accepted its NDA submission for its lead candidate drug, an antipsychotic with a novel mechanism of action, for the treatment of schizophrenia in adults. The same drug was also in pivotal trials both as an adjunctive therapy to existing standard of care agents in schizophrenia and for the treatment of psychosis in patients with Alzheimer’s disease. Karuna also had 5 different drugs in early (pre-clinical and Phase 1) development.
The deal represented a major push into neuropsychiatry for BMS, which had previously spent US$80m to obtain US rights to another company’s preclinical-stage Alzheimer’s disease asset.
3. Merck and Prometheus Biosciences - US$10.8bn
The acquisition of Prometheus gave Merck an entry point into the immunology market. Prometheus was acquired 4 months after announcing two successful Phase 2 results for its lead candidate drug in ulcerative colitis and Crohn’s disease. The same drug was being tested in a Phase 2 trial in systemic sclerosis-associated interstitial lung disease. Aside from this drug, Prometheus was advancing four other candidates for immune-mediated indications.
4. AbbVie and ImmunoGen - US$10.1bn
One of AbbVie’s areas of therapeutic focus is oncology and the acquisition of Immunogen was AbbVie's way of accelerating entry into the commercial market for ovarian cancer. Immunogen’s lead drug, a first-in-class antibody-drug conjugate (ADC) for platinum-resistant ovarian cancer, had received accelerated FDA approval 12 months previously. The drug received full FDA approval 4 months after the acquisition was announced.
ImmunoGen had clinical development programs underway for the same drug to expand into earlier lines of therapy and enter other large patient segments of the ovarian market as well as a separate Phase 2 asset for a rare blood cancer and another Phase 1 asset for ovarian cancer and other solid tumour indications.
5. AbbVie and Cerevel Therapeutics - US$8.7bn
For AbbVie, Cerevel offered a “robust pipeline of assets focused on best-in-class potential for psychiatric and neurological disorders where significant unmet needs remain.” Cerevel’s pipeline was seen as complementary to AbbVie’s portfolio of marketed and clinical-stage neuroscience drugs.
Cerevel's main target asset, emracladine, was a next-generation antipsychotic for treatment of schizophrenia. At the time of acquisition, emracladine was in two Phase 2 trials in schizophrenia that were designed to be registration enabling, as well as a Phase 1 study in Alzheimer's disease psychosis.
In addition to emraclidine, Cerevel had another drug in two Phase 3 studies for the management of Parkinsons disease, another in Phase 2 for treatment-resistant epilepsy and panic disorder and yet another drug in Phase 1 for major depressive disorder.
6. Biogen and Reata Pharmaceuticals - US$7.3bn
Most here will be already familiar with this acquisition. Reata was acquired 4 months after FDA approval of its lead asset, Skyclarys, the first and only therapy for the treatment of the rare neurodegenerative disease, Friedreich’s ataxia. Skyclarys had just entered the US market and was already under regulatory review in Europe.
Biogen's intention was to synergize commercialization of the Reata drug with two of its own drugs for neurodegenerative disorders - Spinraza for spinal muscular atrophy (SMA) and Qalsody for amyotrophic lateral sclerosis (ALS).
In addition to Skyclarys, Reata has one drug in Phase 1 and two other drugs in pre-clinical.
7. Roche and Telavant Holdings - US$7.1bn
In October last year, Roche acquired Telavant Holdings, which was a vehicle company in which Roivant and Pfizer have placed the US and Japanese rights to develop, manufacture and commercialize an experimental drug for the treatment of inflammatory bowel diseases. Promising Phase 2 results in ulcerative colitis had been announced 10 months previously and Roche said it was keen to commence Phase 3 testing as soon as possible. The drug also has potential in Crohn’s disease and so is likely to compete with the drug that Merck acquired in its takeover of Prometheus 6 months earlier.
Roche was driven to a deal by falling oncology sales and major late-stage trial setbacks it suffered in Alzheimer's and cancer immunotherapy the precious year.
8. Astellas and Iveric Bio US - $5.9bn
Blindness and regeneration is one of Astellas’ core therapeutic focus areas. With this transaction, Astellas brought in-house an ophthalmology drug for geographic atrophy secondary to AMD, which had been accepted by the FDA for filing two months previously. The drug had met its primary efficacy endpoint with statistical significance across two pivotal clinical trials and had also received breakthrough therapy designation.
Geographic atrophy impacts an estimated 1.5 million people in the US. Iveric Bio’s drug (since approved) is the first drug approved for the condition.
Astellas said that the acquisition of Iveric Bio would provide a foundation of ophthalmology focused capabilities, including a multi-faceted commercial team, expansive network of experts in the ophthalmology field, established relationships with medical institutions, and the infrastructure and experience to drive its combined ophthalmology business going forward.
It said that the drug would also help plug a hole in future revenues due to a key cancer drug coming off patent.
9. Bristol Myers Squibb and Mirati Therapeutics - US $4.8bn (+ $1bn contingent value right)
BMS acquired Mirati 10 months after Mirati’s lead drug received accelerated approval from the FDA.
The drug, Krazati, is a KRAS GC12 inhibitor and was approved for the treatment of one type of non-small cell lung cancer. In the first 6 months following approval, Krazati had brought in just under US$20m sales.
At the time of acquisition, Mirati was ready to commence Phase 3 testing of Krazati in combination with Keytruda in another type of non-small cell lung cancer and was close to an FDA filing for accelerated approval of Krazati in late-line colorectal cancer. A second drug was due to commence Phase 2 testing in another form of cancer the following year and the US$1m contingent value right was payable if that drug was accepted for filing by the FDA within 7 years.
With three key products due to lose patent protection this decade, BMS was under pressure to boost its near-term revenue and pipeline.
10. Bristol Myers Squibb and RayzeBio - US$4.1bn
BMS further added to its oncology portfolio at the very end of 2023 with the acquisition of RayzeBio, a clinical-stage radiopharmaceutical therapeutics company. RayzeBio’s lead asset was in Phase 3 with primary completion of the trial estimated for mid-2025.
BMS said it was further strengthening its growth opportunities in the back half of the decade and beyond. It also wanted to establish its presence in “one of the most promising and fastest-growing new modalities for the treatment of patients with solid tumours – delivering radioactive payloads to cancer cells in a targeted manner.” In addition, BMS believed that RayzeBio’s actinium-based radiopharmaceutical platform had the potential to be a significant IND engine, generating several therapeutic candidates.
(20min delay)