Maverick Therapeutics, Inc.

A new obesity drug developer from investment firm Versant Ventures is starting up with a deal to possibly sell itself to AstraZeneca.The startup, called SixPeaks Bio,launched Wednesday with $30 million in Series A funding led by Versant and involving AstraZeneca. Alongside the funding, the company also announced a collaboration that will see the British drugmaker provide up to $80 million in financing over the next two years. Over that time, AstraZeneca has an exclusive chance to buy SixPeaks at an agreed-upon price once the biotech is ready to bring its lead drug into human testing.SixPeaks is the product of Basel, Switzerland-based Ridgeline Discovery, one of a few initiatives Versant has hatched over the years to turn academic research into new companies. The company was formed to address what CEO Philip Larsen called a burgeoning problem for popular weight-loss drugs like Wegovy and Zepbound. While those medicines help people quickly shed pounds, lean muscle tissue is lost as well. That issue can be exacerbated by people starting and stopping treatment,which is likely to accelerate the unfavorable effect on body composition, he said.SixPeaks is one of a number of companies among them Regeneron,Biohaven Pharmaceuticaland startup BioAgefocused on preserving muscle mass. The company is making antibody drugs that, like some others in development,target so-called activin receptors, an approach thats shown the potential tomaintain muscle while cutting fat.SixPeaks said its drugs may be effective as monotherapies or alongside the incretin drugs that stimulate the gut hormones like GLP-1. Its also developing a conjugated medicine that combines both approaches, though none are yet in human testing.Larsen declined to share more specifics about SixPeaks' pipeline, but said the company has the “opportunity to reach quite broadly and not just focus on being the companion to GLP-1s.“The deal follows a strategy Versant once favored, in which it would create a startup alongside a prearranged acquisition deal with a specific buyer. These types of build-to-buy, or option deals were tools Versant and some other venture firms used to guarantee returns during a tough investment climate early last decade. But they come with trade-offs, locking a startup into a deal with potentially smaller financial upside than independent growth may offer. In some cases, an acquisition doesnt occur, forcing a young biotech to chart a new course.Versant has moved away from such arrangements since, but they've still been done in recent years, such as with Novartis' recent buyout of IFM Dueand Takedas acquisition of Maverick Therapeutics in 2021.According to Alex Mayweg, a managing director at Versant and chair of SixPeaks board, the company wrestled with which path to pursue after receiving early and intense interest from investors as well as pharmaceutical companies.We had options. This space is attracting a lot of attention, he said.But Larsen noted the huge costs associated with developing cardiovascular drugs, making it critical to execute a a clinical development plan with precision from the start, and getting a partnership fairly early.AstraZenecas drive, interest, capability and motivation to win in this race was extremely strong, Mayweg added.The British drugmaker aims to come from behind in that race,as its most advanced prospects are progressing towards mid-stage testing. But the company has circled cardiometabolic research as a key part of its goal to hit $80 billion in revenue by 2030, and last year, made its intentions clear by licensing an oral obesity drug from Chinese biotech Eccogene.In an investor presentation on Tuesday, AstraZeneca pointed to a number of potential drug combinations for its oral drug and a couple others in development. None of them, though, involved muscle preservation. '

Takeda’s pipeline cull affected assets outside of oncology. Takeda’s vision of becoming a leader in oncology ran into more trouble Thursday when the drugmaker axed (PDF) a midphase immunocytokine and three early-stage CAR-T cell therapy prospects from its R&D pipeline. Under CEO Christophe Weber, Takeda has worked to establish itself as a leader in oncology. But, as the executive said on a quarterly results call with investors, the company has “had some wins ... [and] some setbacks.” The results brought news of more setbacks, with Takeda using the update to reveal it has dropped a clutch of cancer candidates led by modakafusp alfa. Formerly known as TAK-573, modakafusp alfa consists of two interferon alpha-2b molecules fused to an anti-CD38 monoclonal antibody. The idea was to activate innate and adaptive immune cells—while also directly stopping the proliferation of multiple myeloma cells—through targeted interferon signaling. Takeda began a phase 1/2a Darzalex combination trial one year ago, adding to the slate of studies run in support of the immunocytokine, but has now pulled the plug on the program. Andrew Plump, M.D., Ph.D., president of R&D at Takeda, explained the decision on the conference call with investors.  “This is a strategic decision based on a number of factors, including the existing data set, the rapidly evolving multiple myeloma treatment landscape and the long development timelines,” the R&D chief said.  Takeda pushed modakafusp alfa out of the door as part of a pipeline clear-out that also hit three phase 1 autologous CAR-T candidates. Two of the prospects, GPC3-targeted TAK-102 and mesothelin-directed TAK-103, were in development in solid tumors. The third asset, TAK-940, was a CD19-directed, Memorial Sloan Kettering Cancer Center-partnered program that used the 1XX domain to try to enhance efficacy. While Takeda axed a clutch of cancer candidates, Plump said the company “remains committed to oncology and will continue to develop therapies across hematologic and solid tumors.” The R&D chief highlighted the SUMO inhibitor subasumstat, a pair of STING agonists and two T-cell engagers from the Maverick Therapeutics acquisition as candidates to watch.  Plump also cited the appointment of PK Morrow, who joined Takeda from CRISPR Therapeutics last month, as a boost for the oncology unit. Morrow became head of the oncology therapeutic area unit at Takeda, having previously worked as chief medical officer of CRISPR, and held various roles at Amgen. Takeda’s pipeline cull also affected assets outside of oncology. The drugmaker removed three phase 2 drug candidates, namely the rare disease asset TAK-611—which flunked a trial last year—the Parkinson’s disease prospect TAK-071 and the depression molecule TAK-041. In phase 1, Takeda axed treatments for Alzheimer’s disease and nausea as well as a Zika vaccine candidate. Amid the changes, Takeda grew its R&D spend by 7.3%, although Chief Financial Officer Costa Saroukos said that “does reflect some phasing,” and the company is still aiming for a mid single digit increase over the full year. Saroukos made the comment on what looks set to be his last quarterly results conference call as CFO of Takeda.  Milano Furuta, president of Takeda’s Japan pharma business unit, is preparing to take over as CFO in April. Saroukos is leaving because “after 20 years working abroad, I’m ready to move back to Australia to be closer to my family,” the outgoing CFO told investors.

Five years ago this month, Takeda Pharmaceuticals completed a $62 billion acquisition of Shire one of the largest deals in pharmaceutical industry history. The anniversary has resurfaced scrutiny over the buyouts value and mixed results.The addition of Shire grew the footprint of Japans largest pharma, helping it expand into European and U.S. markets. It also bolstered Takedas pipeline and funneled more R&D investment toward vaccines and plasma-derived therapies. And while the company took on about $60 billion in debt to complete the acquisition, Takeda used divestitures to lower its debt burden and exceeded its predicted cost savings a year ahead of schedule.Yet, for all those benefits, Reuters reported in December how the megadeal hasnt delivered value to Takedas shareholders and showcases the risk of high-profile megamergers. And when PharmaVoice sat down with Chris Arendt, the companys chief scientific officer, at the J.P. Morgan Healthcare Conference this month, Takeda was emerging from a fresh cycle of up-and-down news.In October, the company said it was pulling Exkivity, a lung cancer drug, from the market after the treatment failed a confirmatory trial.As challenging and heartbreaking as that is, its kind of how drug development plays out, Arendt said. Thats the reality there will be ups and downs.Weeks later, the company reduced its full-year profit forecast by 36% in the face of pipeline setbacks and patent expirations for major drugs like the ADHD medicine Vyvanse.Yet in November, Takeda won Food and Drug Administration approval of fruquintinib for patients with metastatic colorectal cancer that has been previously treated. Fruquintinib is one of the key drug the companys CEO said would help it rebound in the coming years. At JPM, Arendt was upbeat about the future of Takedas pipeline.Takeda is in a really good place, he said. We are where we want to be this far out from the Shire deal in terms of capabilities and R&D strategies.Living on the edgeArendt came to Takeda from Sanofi in 2015, first as head of immunology, before later leading the oncology cell therapy and therapeutic area unit. As he kicked off his career at Takeda, Arendt, who took over as CSO in October, said the company was embarking in earnest to reshape its therapeutic pipeline and focus on three core areas: neuroscience, gastrointestinal disorders and oncology.In recent years, the company has also leaned into vaccine and PDT development while branching out into new modalities and pursuing partnerships that support those efforts.In particular, Arendt pointed to its $4 billion purchase of Nimbus Therapeutics TYK2 drug in 2022, which delivered positive topline results from a Phase 2b study for psoriatic arthritis in September. The selective TYK2 inhibitor could target multiple immune-mediated inflammatory conditions and, if approved, would go head-to-head with Bristol Myers Squibbs TYK2 inhibitor, Sotyktu.Thats a program were really excited about, Arendt said.On the oncology front, Takeda bought Maverick Therapeutics in 2021 to take hold of its T cell engager pipeline, which involves treatments that use a patients cells to attack solid tumors.We brought in Mavericks T cell focus and married in with our incredible talents and capabilities to further its potential, Arendt said. We love this model of trying to complement what pharma can do at scale with what biotechs do really well.Two other acquisitions in the last few years of GammaDelta Therapeutics and Adaptate Biotherapeutics have also targeted T cell technologies and fit into Takedas strategy of reinventing its oncology pipeline and investing in immunotherapy and antibody-based treatments, Arendt said.Takeda continues to eye other partnerships. Were looking at where pioneering science is emerging, he said. You can look at what other companies are doing and follow the latest press releases into the latest biological space, but we look at the next step changes, and try to advance whats cutting edge.Takedas outlookNone of these changes are to suggest that Takeda is straying completely from its roots in small molecules.Any good investment portfolio needs to be balanced to level the risk and were always considering that, Arendt said. You can look at some of the cutting-edge modalities in cell therapies, but were also still interested in small molecules [to create] a balanced portfolio strategy.What will all of this amount to in 2024?Our transformation was about planting the seeds, Arendt said. A lot of our R&D was seeding and now its maturing 2024 is about bearing fruit in terms of clinical readouts.This year will also mark an overall shift in Takedas pipeline from being historically weighted toward earlier-stage programs to having more in later-stage development, Arendt said.With the launch of newly approved drugs underway, the TYK2 drug moving into Phase 3 trials, a drug development engine thats churning hard the company recorded $4.8 billion in R&D investments in 2022 and an eye out for new partnership opportunities, Takeda isnt done with its latest reinvention.Well surprise you with more deals you may not have seen coming, Arendt said. '