All the biopharma world is talking about right now is M&A. Who’s going to buy? How much are they willing to spend? Who’s going to get bought?
So here are our predictions for the year, which has, so far, seen absolutely zero major acquisitions but plenty of licensing deals and research collaborations as Big Pharma takes a more hands-off approach to business development. That’s despite many professing their M&A chops in earnings calls and boldly declaring the power to buy—we’re looking at you, Pfizer.
We know the drought has to break at some point, and a recent prediction said the monsoon would likely begin in March.
Whenever it happens, we see this collection of 10 companies as the likely targets. These companies have been discussed in a handful of analyst reports and flagged by investment banks as likely to be sold.
One of our favorites on the list—and perhaps one of our wildest predictions—is Vertex Pharmaceuticals, the cystic fibrosis leader that has been mentioned as a likely buyer and potential target. A few Big Pharmas have the cash firepower to ink a deal like this (Pfizer), with Vertex valued in December around $61 billion. Execs have been predictably mum on the size of deals they’re craving.
But then again, Vertex could just buy its own company, likely CRISPR Therapeutics. The two companies already have a major partnership on new cystic fibrosis meds.
Read on to hear about why we think these 10 companies are coming to a headline near you—any day now, we hope. For more on what's to come in 2022, check out our report here.
Adaptimmune
At first glance, Adaptimmune looks to have the world at its feet. Recent months have seen the TCR T-cell therapy specialist land a deal with Roche— worth $150 million upfront and up to $3 billion on the back end— and deliver clinical trial data that put it on track to win a landmark FDA approval. Yet, that progress has failed to translate into lasting growth in Adaptimmune’s share price.
With Adaptimmune’s market cap languishing below $500 million, will a buyer make a move for the biotech?
The answer to that question may depend on whether Adaptimmune can deliver data that can quell lingering doubts about its technology. Evidence that MAGE-A4 TCR T-cell therapy afami-cel, which Adaptimmune will submit for approval in sarcomas this year, triggers durable responses could go some way to improving sentiment, but the R&D focus is already turning to follow-up candidates.
Adaptimmune has a next-generation MAGE-A4 drug, featuring a CD8α co-receptor to improve efficacy, that is making its way toward clinical trial readouts. The prospect triggered responses in 36% of people in a phase 1 trial that is enrolling patients with a range of solid tumors. The questions now are how durable the responses will be and how the drug will fare in phase 2 trials in esophageal and ovarian cancer.
Work is also underway to evaluate the therapy in combination with a checkpoint inhibitor. Adaptimmune has yet to say much about the study, beyond the fact that it is slated to start this year, but evidence the therapy works well with the dominant treatment of many cancers could open up more M&A opportunities.
Only some of the data will arrive this year. Adaptimmune plans to release full data from the first clinical trial of its next-generation MAGE-A4 candidate at ESMO, but updates on the two mid-phase studies are scheduled for 2023.
As such, the data that could make Adaptimmune a more compelling takeover target may arrive too late to trigger a deal in 2022. But the recent progress of Adaptimmune’s pipeline deeper into the clinic means the company is now in a critical period in which it could deliver data that proves the doubters right—or sees it emerge as the biotech that cracks the solid tumor cell therapy conundrum.
Alnylam
Yvonne Greenstreet recently took over as CEO. Could one of her first major acts be leading the RNAi specialist to a takeover?
It’s been less than a month since Greenstreet, previously president and COO, took the reins from John Maraganore, Ph.D., and Alnylam has already been singled out as a top M&A target for the year. Goldman Sachs and Bloomberg both mentioned Alnylam in their predictions, with Novartis as the most likely buyer.
Alnylam and Novartis initially partnered in 2005, but that deal ended on a bit of a sour note when Novartis departed in 2010 and left Alnylam with a hard recovery. Now, they’re back in business together.
The Swiss giant started a three-year collaboration with Alnylam earlier this month for a liver failure treatment. The deal may signal an interest in acquiring the smaller biopharma in the near future. This came on the heels of the FDA’s approval for Leqvio, a high-cholesterol treatment Alnylam developed and later sold development, manufacturing and commercialization rights to Novartis in 2019.
Another company spotlighted as a potential buyer is Regeneron Pharmaceuticals. Alnylam and Regeneron have been collaborating since 2019 on finding and developing treatments for a range of ocular and central nervous system diseases. Outside of its collaborations, Alnylam submitted a request in December 2021 to start a clinical trial for a potential Alzheimer’s treatment. This is obviously in very, very early stages, but it could make Alnylam more appealing to Regeneron, which has worked on Alzheimer’s in the past.
There’s also been a flurry of interest in Alzheimer’s in general since the FDA approved Biogen’s Aduhelm, with many major pharmaceuticals revisiting the neurodegenerative disease.
In addition, Alnylam is neck-and-neck with a host of companies developing treatments in the rare disease transthyretin amyloidosis (ATTR). A few drugs are already approved for some types of the disease, including Alnylam’s Onpattro, and the company is working to offer another option for a different subset of patients.
But a setback for rival BridgeBio in December has put Alnylam back on its heels, with analysts wondering if Onpattro will clear the study. A readout is expected this year.
BioMarin
As BioMarin rolls out its biggest product launch ever and nears the finish line for a bleeding disorder gene therapy, pharmas could come knocking on its door. And answering that door could be a board member with experience sealing one of the largest pharma mergers in history.
Beyond its seven products already on the market, BioMarin could also soon offer a buyer access to a hemophilia A gene therapy, should U.S. and EU regulators greenlight ValRox. The treatment is already under review in the EU, and a recent phase 3 win means it will head to the FDA in the second quarter.
RBC Capital Markets analysts think ValRox will finally make the market this time around. The FDA rejected it in 2020 on durability concerns and requested data on a new primary endpoint. BioMarin announced ValRox had met the new goal, a two-year annualized bleeding rate, in a phase 3 trial in January. That was well in advance of Pfizer and Sangamo Therapeutics' phase 3 trial, which the companies voluntarily paused last year for changes to the protocol.
While biopharmas might be on the hunt for biotechs that need help bridging the clinic with commercialization, BioMarin could be attractive for its market experience, giving buyers immediate revenue. BioMarin's latest approval, Voxzogo, is the first FDA-approved treatment for children with achondroplasia, which inhibits linear growth in children. The treatment also secured European approval last summer.
CEO Jean-Jacques Bienaimé said Voxzogo could become the biggest launch in the "history of the company."
Speaking of history, ex-Celgene CEO Mark Alles joined BioMarin's board on Jan. 1. He of course helped ink Celgene's major $74 billion merger with Bristol Myers Squibb in 2019.
With that record-breaking deal on his resume, Alles can surely tap into his network and influence a BioMarin exit. The California biopharma has seen its share price ebb and flow from a 2021 low of $71.72 in October to nearly $85 apiece in January.
After the hemophilia A prospect, BioMarin has two gene therapies and a small molecule in phase 1 trials. The rest is preclinical. To beef up that earlier-stage innovation, BioMarin linked arms with Skyline Therapeutics for a multi-year cardiovascular gene therapy collaboration in December.
CRISPR Therapeutics
Once buyers get beyond CRISPR Therapeutics' logo, which looks eerily similar to Pantone's, they'll be seeing green.
That's cash, of course. The color comes in hues, or a variety of money-making possibilities. For gene editing biotech CRISPR, the first shade is a $900 million upfront pact with cystic fibrosis drugmaker Vertex. The duo hopes to beat bluebird bio to market with a gene editing therapy for sickle cell disease and beta thalassemia, two inherited blood disorders. CRISPR stands to earn another $200 million in the tie-up.
CRISPR, which was co-founded by CRISPR co-pioneer Emmanuelle Charpentier, could offer biopharmas a pipeline of treatments for popular oncology indications that are being targeted by cell therapies, which remain an attractive treatment class. CRISPR's cell therapy work includes two CAR natural killer cell candidates in partnership with Nkarta.
The biotech also has multiple research-stage in vivo programs that could provide some assets for Big Pharmas hoping to bulk up their pipelines as we near 2030. Gene editing has been high on the list for many of the major companies that have publicly stated they are hunting for M&A this year.
One potential buyer is long-time partner Vertex, an idea that has been flagged by numerous analysts. Vertex would provide the commercialization expertise, and CRISPR would contribute its innovation.
Not far into due diligence, though, potential acquirers will see a few red flags: the gene-editing biotech fired its executive vice president of research and development Tony Ho, M.D., with few details in December. Further yet, one of the first 11 patients to receive the biotech's CAR-T cell therapy died in October 2020.
Investors have also questioned the durability of CRISPR's CAR-T therapy in patients with B-cell cancers, even though the treatment sparked responses in 58% of patients.
Ionis Pharmaceuticals
Ionis’ partnerships are a who’s who of Big Pharma: a new $2.9 billion tie up with AstraZeneca, plus deals with GlaxoSmithKline, Biogen, Bayer, Novartis—and the list goes on and on.
The RNA-targeting biotech is clearly on the pharmaceutical industry’s radar. With a sharp appetite for deals among the industry's heavy hitters, this could be the year one of them pulls the trigger to take Ionis home.
So why is Ionis the coolest biotech on the block? The California company has developed a drug discovery platform that targets RNA to create new antisense therapies. Ionis’ goal is to stop the formation of disease-linked proteins before the process even starts, therefore preventing disease in the first place. It's an idea that has caught on across pharma as companies tackle the underlying causes of disease, rather than just their symptoms.
Ionis already has three therapies to its credit: Spinraza, which was developed in partnership with Biogen, is approved in the U.S. for treating spinal muscular atrophy—a disease that never had a treatment option before Ionis came along. The second U.S.-approved med is Tegsedi, which is marketed by Ionis unit Akcea; it treats patients with the polyneuropathy form of hereditary ATTR amyloidosis. Finally, there’s Waylivra, a treatment for familial chylomicronaemia syndrome (FCS) that is only approved in the EU.
In the pipeline, Ionis has more meds to come for ATTR amyloidosis and FCS, plus severe hypertriglyceridemia, amyotrophic lateral sclerosis (ALS) and more.
One ALS med in the works, tofersen, made the news last year amid public pressure for partner Biogen to offer the option to patients outside of clinical trials on a compassionate-use basis. The pharmaceutical company originally declined, but it caved to pressure in April and offered tofersen to patients with a certain form of the neurodegenerative disease. The drug is currently in phase 3 testing for that disease.
A hopeful sign emerged for Ionis in January when Roche decided to revisit their partnered drug tominersen, which failed a phase 3 clinical trial for Huntington's disease in 2021. The Swiss pharma decided to revert the program back to phase 2 to examine whether it may benefit younger adult patients with a lower disease burden.
Ionis has signed a flurry of deals in recent months, including an opt-in from Biogen in January to develop another genetic disease treatment through their earlier partnership in neurological disorders. And in December, AstraZeneca put $2.9 billion in biobucks on the line for work on the heart disease drug eplontersen.
With Biogen desperate to plug the leak in its pipeline—and the tidal wave of pushback to Alzheimer’s med Aduhelm—perhaps Ionis could be an attractive option.
Karuna Therapeutics
Karuna Therapeutics is at a critical juncture. Several years after it began getting the old xanomeline gang back together, the biotech is closing in on data from two phase 3 clinical trials in schizophrenia. Success will make Karuna that rarest of things: an independent biotech with a validated psychiatric disease drug.
Eli Lilly went some way to validating the efficacy of M1/M4 agonist xanomeline in the 1990s, linking the drug to improved cognition in Alzheimer’s patients before tolerability problems sank the asset. Karuna paid Lilly $100,000 for rights to the drug in 2012 but stayed below the radar in its early years.
That changed in 2018 when Karuna began hoovering up cash and researchers who worked on xanomeline at Lilly ahead of clinical trials for a co-formulation, KarXT, designed to mitigate the tolerability problems.
Karuna made schizophrenia, not Alzheimer’s, its first focus. Today, the company is just months away from revealing if its attempt to resurrect xanomeline has paid off. Data from one phase 3 trial are due around the middle of the year, with the readout of a second study set to follow in the second half of 2022.
Positive safety and efficacy data from the two clinical trials could take Karuna, a biotech that already has a $3 billion market cap, to another level and get potential biopharma buyers off the sidelines. Karuna is also equipped to take KarXT forward itself, though, with the almost $500 million in cash in its coffers as of the end of September—enough to see the biotech beyond a filing for approval in schizophrenia.
Success in schizophrenia alone would be enough to make Karuna a prized target. And the company has another ace up its sleeve in the form of a phase 3 program for psychosis in Alzheimer's set to start this year. While KarXT isn’t the long-awaited magic bullet for Alzheimer’s, the clinical data gathered to date suggest it may be a boon for the many patients who develop symptoms of psychosis.
Karuna will pocket the lion’s share of any revenues generated by KarXT. The Lilly deal features $16 million in regulatory milestones and $54 million in commercial paydays, plus low to mid-single-digit royalties.
Mirati Therapeutics
Mirati is a real David vs. Goliath story, as the small biotech goes up against Amgen in KRAS-mutated cancers. This begs the question: Would Mirati agree to a buyout to get some Big Pharma backing as adagrasib moves closer to the market?
Merck & Co. has been named as a natural choice to pick up the California biotech. The Keytruda maker is looking to bulk up its cancer pipeline with several products that can eventually take over for the megablockbuster. Keytruda is projected to reach $27 billion in 2026 sales, but its patent protection will end in 2028, so Merck is hunting for deals to prepare.
Adagrasib is a KRAS inhibitor awaiting regulatory approval from the FDA in non-small cell lung cancer, which would see the therapy follow Amgen’s first-to-market Lumakras. KRAS cancers used to be considered undruggable, but Amgen broke the mold when Lumakras was approved last year. Mirati has been plugging away behind them with a therapy that has shown success in places the Big Pharma’s asset has not.
Mirati recently posted some results from a clinical trial featuring patients with pancreatic and GI tumors, which provided a nice data boost in an indication Amgen has not tried yet.
Analysts have predicted that adagrasib could reach blockbuster status itself, with $1.74 billion in sales by 2026 just in the lung cancer indication. But Mirati's drug has also seen success in colorectal cancer, where Lumakras has struggled. This indication could drive adagrasib sales up to $3.84 billion in the U.S. and EU.
The therapy is already in testing in combination with Keytruda. Mirati tweaked the dose in that mid-stage trial last year to try to improve tolerability.
Adagrasib is easily Mirati’s lead product, but the biotech has one other late-stage asset in the multi-kinase inhibitor sitravatinib, now in lung cancer trials as a booster for checkpoint inhibitors to overcome immunotherapy resistance. Other assets include MRTX1719, which is in pre-clinical testing for MTAP-deleted cancers, and two preclinical assets for solid tumors.
Mirati underwent a leadership change last year as David Meek succeeded Charles Baum, M.D., Ph.D., as CEO. Meek quickly shook up the senior leadership, showing the door to Chief Medical Officer Joseph Leveque, M.D., and Chief Operating Officer Daniel Faga.
Sarepta Therapeutics
Sarepta has been rumored as a buyout target for years, with Biogen once considered the ideal buyer. Many analysts figured the biotech was sure to be snapped up when Exondys 51 was approved for Duchenne muscular dystrophy back in 2016.
And yet the company has hung on, stayed independent and continued to add new DMD treatments to its expansive pipeline.
Sarepta is a clear leader in DMD, with three approved treatments—Exondys 51, Vyondys 53 and Amondys 45—plus an additional 20 therapies under development, including three gene therapies and two gene-editing candidates.
But the field is notoriously difficult and has challenged much larger pharmaceutical companies. As Sarepta has pushed to develop next-generation treatments, or those that can tackle different types of the devastating disorder, the clinic—and the markets—have not always been kind.
Sarepta’s shares dropped 15% in early January on a trial update for SRP-9001 that showed the gene transfer therapy spurred statistically significant improvements in a functional motor ability test. Announcing the results at the J.P. Morgan Healthcare Conference, Sarepta also said the treatment would be headed for regulators as soon as next year. Analysts were unimpressed, noting that the data was sure to cheer believers, but unlikely to sway the “doubters."
The company has also reported some troubling adverse events for other candidates, such as the May 2021 report that two patients taking SRP-5051 experienced critical drops in magnesium and potassium levels.
And Sarepta is not alone in facing challenges in the incredibly difficult disease. Pfizer’s DMD gene therapy program has met a number of obstacles, including a recent patient death that sent the Big Pharma back for some soul-searching about its next steps.
Beyond DMD, Sarepta is not a one-trick pony; it counts treatments for multiple sclerosis, cardiomyopathy, Pompe disease and others in its pipeline. The most advanced assets are three gene therapies in limb-girdle muscular dystrophies, a muscle-wasting disease similar to DMD.
Meanwhile, the company dropped a gene therapy for the neurodegenerative lysosomal storage disorder mucopolysaccharidosis type IIIA, which was being developed in partnership with Lysogene, ahead of a pivotal data release in January. The therapy had struggled through a phase 2/3 trial with the death of a patient and a clinical hold.
Perhaps this next phase of Sarepta’s history would be easier with a Big Pharma backing them up?
uniQure
Gene therapy makers are high on buyers' shopping lists—particularly companies that can offer a near-to-market pipeline options—and UniQure can potentially deliver just that with a late-stage asset that's racing Pfizer to market. But FDA concerns and an early-stage pipeline could make this biotech a bit of a riskier bet.
The biotech’s crop of preclinical assets and an early stage gene therapy in a rare neurodegenerative disorder might catch the eye of biopharmas looking to shore up pipeline holes in the second half of this decade. The company could be particularly enticing to those looking for neuroscience assets.
The Dutch biotech and partner CSL Behring plan to ask the FDA and EU to approve their hemophilia B gene therapy in the first half of this year after it improved annualized bleeding rates in a phase 3 trial. If U.S. or European regulators greenlight the therapy based on that pivotal win, uniQure could be quarters or years ahead of Pfizer’s therapy, for which late-stage data has been delayed until next year.
UniQure’s therapy, etranacogene dezaparvovec, comes with some baggage: the FDA held up the phase 3 trial in December 2020 after a patient was diagnosed with cancer but allowed uniQure to resume the study by late-April 2021. The type of viral vector used to deliver the therapy has also sparked safety concerns in approved meds, leading to a two-day FDA advisory marathon.
uniQure itself has been in the deal hunt recently, so management has experience in all things M&A. The biotech consumed French gene therapy company Corlieve Therapeutics for $55 million upfront last year.
That could be a sign uniQure is in need of external innovation. The biotech's wavy stock performance could mean lower valuations. Once at a peak of $82 per share in June 2019, uniQure tanked to $37 in February 2021 and now sits near $16 apiece.
A uniQure buyer could also tap into a partnership with Bristol Myers Squibb for up to four gene therapies in cardiovascular diseases. But the initial $50 million upfront collab from April 2015 has so far borne little fruit and remains in the preclinical stage. BMS hasn't mentioned uniQure in Securities and Exchange Commission filings since February 2020.
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