Poseida Therapeutics, Inc.

Roche has a big problem. With competition threatening some of its older and most lucrative biologic drugs, the Swiss pharmaceutical giant expects that, in three years time, sales from these assets will decline by roughly $8 billion.Despite this looming danger, Roches leaders have, at least publicly, put on a brave face. Theyve reshaped the companys structure and research priorities, and assured shareholders that new products and a handful of experimental medicines should more than make up for the financial losses. Some of those assets were developed internally, but others came from a recent tear of dealmaking.Since the summer of 2023, Roche has inked three acquisitions worth more than $1 billion including the $7.2 billion purchase of Televant and entered into a laundry list of licensing agreements and research pacts. Those smaller deals include a partnership with AI chipmaker Nvidia, several bets on genetic medicines, as well as investments into hot areas of science like protein degraders and a class of cancer therapies known as ADCs.Critical investors could argue Roches dealmaking is a bit scattered. The companys main interests span five research fields, from oncology, immunology and neuroscience to cardiometabolic and ophthalmology. But perhaps expectedly, Boris Zatra, the longtime head of business development for Roche Group, doesnt see it that way.We make sure we try to look at everything that's available, Zatra said. The art is to make sure your funnel is efficient. You don't want to miss something, but you also cannot boil the ocean.Zatra, who Roche appointed as head of corporate business development last year, spoke to BioPharma Dive about the tenets of the companys dealmaking strategy. He also explained why Roche hasnt done supersized acquisitions lately, and how it plans to tap into the rapidly advancing Chinese biotechnology market.The following conversation has been edited and condensed for clarity.BIOPHARMA DIVE: You were Roches head of business group development for 12 years, a period which brought the rise of immuno-oncology, the ups and downs of cell and gene therapy, and, more recently, a bit of a resurgence in neuroscience and a huge push into obesity drugs. How has Roches BD strategy changed over that time?BORIS ZATRA: I'm not sure the strategy would have changed. The biggest change I witnessed is the reorganization we did last year, where we decided to bring my team and the partnering team into one team corporate business development which basically provides under one umbrella end-to-end BD capabilities.Why did we do that? There are internal factors and external factors. On the internal side, youve heard of our One Pharma strategy, the bar on R&D excellence. We went through quite a long process to make sure we really define what we are after. Our ambitions are clear. They are high.On the external side, what I would say is the innovation across therapeutic areas, across modalities, across geographies is very exciting, but that's a huge space to search. It's really important to be structured, to be systematic, to be rigorous, to make sure that everybody knows how they fit, what we want to do, what's our risk appetite.All things being equal, executing a deal today is probably more challenging than it was four or five years ago. It's more complicated, it's more competitive, it's more expensive, it's more intimidating, its more sophisticated.Outside of Televant, Roche hasnt made a $5+ billion acquisition in quite some time. In fact, the company seems much more interested in smaller research partnerships. Do you see the average size of your deals changing anytime soon?ZATRA: If you look at our size as a company and our financial means, yes, it's been a while since we have been in a deal environment where we would max out. I think that's been a constraint.In terms of looking ahead: if you take 2023 and 2024, I think that's a relatively good representation of what we aspire to continue doing. 2023 with Carmotand Televant, you have more late-stage, building up capabilities in an accelerated way. In 2024, it was a bit more spread. Regor was Phase 1 oncology, CDK4/6 with ADCs.There is recognition that we also have to take a portfolio approach. We have to invest in early-stage, mid-stage and late-stage.By design, you would want to place many more bets at an early stage, because it also takes more of those to make it all the way through. We clearly aspire and hope that we will be doing deals across the spectrum.A sign with the Roche logo stands in front of a tall building.Permission granted by RocheAn analyst once told me that larger, acquiring companies have an internal ceiling for things like premiums. Your Poseida deal had a premium over 200%. Do premiums and things like that influence your teams BD decisions?ZATRA: The answer is yes and no. When we do deals, we have to be comfortable with the valuation we pay. Youre referring specifically about public deals. In the case of public deals, you have a price reference, and then there is a premium being paid. If the deal happened, it means the seller and the buyer reached an agreement on price.We're sophisticated players. We look at trading multiples. We look at transaction multiples of similar deals. It's not always easy, but at least weve got benchmarks. We do the bottom-up valuation, really looking at the prospects, the platforms, the compounds, assuming they make it all the way to market with the probability adjusted. We do a deal where we can justify the value.There is a benchmark for premium. Typically, you will pay the average, which is in the 60% to 80% branch. Where the data gets a bit more complicated with respect to premium is when you get into smaller [deals]. First, the comparisons are a bit more complicated. And when you get to the sub-$1 billion market cap, then youve got liquidity [considerations].The smaller deals tend to attract sometimes some of the highest premiums. That's because perhaps the valuation attributed by the market was not fully reflective of the intrinsic value of the asset.One trend thats accelerated is the number of deals involving assets from China. Roche itself recently inked deals with the Chinese biotechs Regor, Innovent and Zion Pharma. Whats driving this, do you expect it to continue and how will it impact biotech in the U.S.?ZATRA: China is establishing itself as the second largest place of innovation outside of the U.S. We saw an inflection point last year, which was really outlined by the deals which happened. And it was not only the deals which happened in 2024, but also, if you take the example of bispecifics, the PD1/VEGF [drugs]. You had the Akeso-Summit relationship and the readouts, which put a huge focus on what's happening in China.I don't know if this will change, but my sense is: to create innovation, you need to create an ecosystem. You need the entrepreneurs, you need the capital, you need the science, you need the universities. You need all that ecosystem to work in a very synergistic way. You don't create that out of nowhere. So when it happens, to that level of maturity, my sense is this is pretty real and pretty solid. I don't think this will necessarily change.The trend I'm seeing more is people wanting to ensure they are equipped to screen and to tap into that market. Because it is a bit more complicated. That market is not highly intermediated. The opportunities they are not in databases. You really have to go on the ground. And if you take a given target, you have potentially 10, 20 companies working on that target. So then, the art becomes to know all of those companies, and then to filter through which of those are really interesting.To exploit the potential of that market, from a BD perspective, you need to be equipped for that. It's less interrogated, less sophisticated, less mature, probably, as a BD market than the U.S. is.One of the main areas people think of when they think of Roche is oncology. What do you see as the role for these emerging PD-1/VEGF drugs? Are you convinced theyll be the next big thing in immunotherapy?ZATRA: It's very difficult to comment. What is for sure is some data that has been published has been very impressive. The questions we need to answer are: Do we understand exactly what is happening? What exact mechanism? Because those components are not new. VEGF is not new. PD-1 is not new. So what makes it so special when you bind them the way they've been bound as bispecifics?There are now tens of companies getting into this space. Unless I'm wrong, I don't think there's been a lot of disclosure of overall survival data. Clearly, as we know in that space, overall survival will always be very important.I think it's very exciting, and let's see how things unfold. I think maybe later this year, at latest, there will be more data that will shed a better light as to how big of an opportunity these will be for patients. '

Roche is actively looking at deals across all therapeutic areas, its pharma chief Teresa Graham said.\n Roche has about $10 billion in M&A firepower it can deploy every year, but it’s “not just going to spend money,” the company’s pharma CEO Teresa Graham said at the J.P. Morgan Healthcare Conference.Roche is fully ready to deploy the money “if and when we find transformative assets that are either complementary to our portfolio or, again, change the game in important diseases outside of those focus areas,” Graham said Monday.The Swiss pharma didn’t spend that much on business development last year, J.P. Morgan analyst Richard Vosser noted during the Q&A session of Graham’s presentation.Last fall, Roche unveiled a new pharma strategy, placing a focus on the five therapeutic areas of neurology, oncology/hematology, immunology, ophthalmology and CVRM (cardiovascular renal metabolic).Some of Roche’s recent deals in these focus areas include an antibody-drug conjugate pact with Innovent Biologics, the $1.5 billion acquisition of off-the-shelf CAR-T partner Poseida Therapeutics, the purchase of Wnt signaling-focused biotech AntlerA Therapeutics and the $850 million upfront licensing of a portfolio of CDK inhibitors from China’s Regor Pharmaceuticals. As Graham noted Monday, Roche has had a strong presence in China and will continue to look for assets in the country.Roche wants to get in on differentiated assets with the potential to help a large number of patients around the world, Graham added. Roche recently took a hard look at its internal pipeline, a process that led the company to discontinue about 30% of its pipeline so far, according to Graham. Still, the company expects its R&D spending to remain flat in 2025; while Roche will “continue to be very disciplined” in resource allocation, it will also make sure to maintain sufficient investments in its research programs, the exec said.“As we’ve culled so many things out of our portfolio, we have freed up a lot of oxygen to actually invest in new programs that may be internal or external,” the Roche exec said.According to Graham, Roche\'s late-stage program will look “materially different” in 2026 than it is today; about 18 programs may enter late-stage testing or graduate from that phase in the next 18 months.But, as is always the reality with drug development, not all Roche candidates, including those in-licensed, may succeed as planned. During Monday’s presentation, Graham said Roche is not giving up on its Prothena-partnered prasinezumab in Parkinson’s disease despite a phase 2b flop disclosed in December. While the PAVODA trial missed its primary endpoint of time to confirmed motor progression, Roche has noted a more pronounced effect for the anti-alpha-synuclein antibody in levodopa-pretreated patients.“Given the high level of unmet need for these patients, we decided that the important thing to do is to let the [open-label extension] data mature a little bit longer before we actually take a decision on where we wanted to head” with prasinezumab, Graham said during her presentation.Roche wants to thoroughly evaluate the results and make a data-driven decision. The company will be able to share more later this year, Graham said.

Astellas remains committed to Xyphos’ Advanced Cellular Control through Engineered Ligands (ACCEL) technology, a company spokesperson said. \n On Astellas Pharma’s mission to develop new cell therapies in cancers and other diseases, not all candidates are destined to reach the finish line. Now, following a review of its pipeline, the Japan-based drugmaker has jettisoned an early CAR-T prospect leveraging technology from its subsidiary Xyphos.The asset in question, an autologous CAR-T dubbed ASP2802 aimed at CD20-positive B-cell lymphomas, had been undergoing a phase 1 trial to determine a suitable dose for further studies as well as the candidate’s tolerability and safety. But an Astellas spokesperson confirmed to Fierce Biotech that “as a result of our prioritization efforts, we have made the difficult decision to terminate ASP2802.”“Astellas is continually evaluating how to streamline its operations and prioritize its resources in our continuous effort to deliver meaningful solutions to our patients,” the spokesperson added.They also noted that the work done on ASP2802 has yielded “important progress” and “drug development knowledge” that will benefit the company’s efforts in other disease areas. Additionally, Astellas remains committed to Xyphos’ Advanced Cellular Control through Engineered Ligands (ACCEL) technology, the spokesperson said.Word of the study\'s termination was first reported by Endpoints News.  Astellas paid $120 million upfront to acquire Xyphos in 2019. As part of the pact, Xyphos is also in line to receive potential development milestone payments that could work out to a total deal value of $665 million, Astellas said at the time.The transaction allowed Astellas to get its hands on Xyphos’ synthetic biology platform, which, in the case of CAR cells, leverages an engineered modification to a natural human receptor known as NKG2D. Through protein engineering, Xyphos has modified several natural ligands of NKG2D, allowing them to be wed with tumor-seeking antibodies among other functional molecules.In turn, CAR cells leveraging this approach can be directed by the ligand-bound antibody to seek, become activated and attack a targeted cancer cell, Astellas and Xyphos have said previously.In the case of ASP2802, which was developed using Xyphos’ technology, the CAR-T prospect was accompanied by a so-called MicAbody protein designed to direct and activate the CAR-T component.Despite the decision to scrap ASP2802, Astellas has stayed busy inking cell therapy deals through Xyphos in recent months. Xyphos linked arms with Kelonia in February 2024 for a research and licensing deal worth more than $800 million. The accord saw the companies combine their technologies to work on up to two programs in immuno-oncology, with the second contingent upon Xyphos opting in.Three months later, Xyphos signed a deal with Poseida Therapeutics to develop two cell therapy candidates for solid tumors that will fuse Poseida’s allogeneic CAR-T platform with Xyphos’ ACCEL technology.Aside from ASP2802, Astellas is working on a wide range of cell therapies seeking to tackle cancers, vascular disease, autoimmune diseases and more.