FDA, AbbVie + DJS, Roche + Hookipa, Kyverna

Some statistically significant guidance, seed to acquisition, some biobucks, and the CART of the future.

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Story References
FDA
AbbVie + DJS
Roche + Hookipa
Kyverna

About the Show
Life Science Today is your source for stories, insights, and trends across the life science industry. Expect weekly highlights about new technologies, pharmaceutical mergers and acquisitions, news about the moves of venture capital and private equity, and how the stock market responds to biotech IPOs. Life Science Today also explores trends around clinical research, including the evolving patterns that determine how drugs and therapies are developed and approved. It’s news, with a dash of perspective, focused on the life science industry. 

Transcript

Introduction

Welcome to Life Science Today, your source for stories, insights, and trends across the life science industry. I’m your host, Dr. Noah Goodson. This week, some statistically significant guidance, seed to acquisition, some biobucks, and the CART of the future. 

Disclaimer

The views expressed on Life Science Today are those of the host and guests. They do not necessarily reflect the opinions of any organizations with which they are affiliated. 

FDA Guidance

Last week, the FDA released critical and long-awaited guidance on assessing the efficacy of multiple endpoints in clinical trials. To break this down in the simplest terms, you have to first understand that clinical trials are built to test outcomes of a therapy or medical devices impact calls endpoints. These are divided into primary endpoints (the main thing a study wants to assess) and secondary endpoints (other things that might also be relevant to the study). To address these endpoints a range of validated mechanisms might be utilized within a study. For example, if a condition impacts your heart health and function by changing your cholesterol levels, a drug targeting this would need to show via a blood test that cholesterol levels were decreased and through heart monitoring that your heart health improved as a result. These might be primary endpoints with secondary endpoints being, weight loss, or improved blood pressure. Ok fairly simple on the surface, except it is completely not simple below the surface. First, for many conditions there are not totally clear measures of clinical effect. Think of something like Alzheimer’s, there are lots of tests that indicate cognitive decline, but the disease impacts lots of areas of brain health, and a drug may help some of those areas (say memory of events) but not others (word recall). Additionally, some tests might have overlapping testing criteria, think two memory tests that test related concepts. When you start layering complex methods together to determine if a drug is effective it can be challenging not just at design the right methods and testing them, but also in statistically analyzing them in a way that prevents making errors. 

Now the guidance starts out with some pretty pragmatic statistical approaches. It’s largely statistics 101, but for the sake of the show I won’t go too far into the details. The important piece here that impacts the life science industry is that the FDA is laying out guidance about how statistics, populations sizes, multi-component endpoints, and multiple endpoints, and more should be pre-accounted for in a statistical plan. The point for those building and conducting clinical trials is that you need to have a specific plan for how you are going to be assessing the data and account for two critical components in that statistical plan, 1) how you are avoid Type 1 Errors (when you think the drug works but it doesn’t) 2) How you account for Type 1 Errors when there are multiple endpoints which may compound probability of making a Type 1 error. 

Like many guidance’s from the FDA there is little dogma beyond mentioning commonly accepted statistical thresholds. The real concern here is that as Sponsors are preparing their studies and coming to the FDA there is agreement upfront about what success looks like and how that is being measured to prevent surprises and lengthy contentious determinations (see Biogen’s Aduhelm for example). Practically, this does mean studies with complex multiple-endpoints, which are growing in frequency with the expansion of precision medicine and rare disease therapies, in those studies additional efforts may be required in the protocol’s statistical analysis plan to account for Type 1 error avoidance during data analysis. And the FDA is signalling you’ll need to account for this upfront before you run your trial, not just on the backend calculations. 

AbbVie Acquires DJS Antibodies for $255M

AbbVie has acquired DJS Antibodies for $255M in cash. The UK based biotechnology company has a small early stage pipeline of therapies, with their lead candidate targeting LPAR1 to treat  Pulmonary Idiopathic fibrosis. The underling value here is that DJS appears to have developed a strategy for targeting complex transmembrane proteins using their HEPTAD platform. They have generated a seemingly effective means of targeting G Protein-Coupled Receptors using antibodies. This combination of immunology and antibody design could be a huge asset as AbbVie looks down the pipeline at the future of targeting immune therapies. For DJS coming off a $6M seed round just under 2 years ago this is massive ROI. Time will tell how AbbVie uses this technology and pipeline going forward. 

Roche & Hookipa Come To a $950M Understanding

Roche has signed a licensing agreement worth up to $950M with the Austrian company Hookipa Pharma to license and develop their therapy HB-700 targeting KRAS-mutated cancers. Like many of these deals in the past, the future numbers are huge, but the initial payment is just $25M. Still the vote of confidence certainly won’t hurt Hookipa. For Roche’s part, they appear to be willing to take another bet on KRAS related conditions. Now this has long proven a challenging target in oncology, so whether Hookipa has cracked that nut or not remains to be seen. For Roche this all stacks up to a relatively small early bet on a Phase I oncology asset. Very business-as usual. 

Lupus CAR-T News

Kyverna Therapeutics has gone to the FDA with an IND application to test the efficacy and tolerability of their CAR-T therapy for lupus nephritis, KYV-101. We don’t normally cover INDs on this show because there are quite frankly a lot of them that don’t ever amount to much – but this particular instance is well worth considering for a variety of reasons. Leveraging the CART approach to treating autoimmune diseases has been under investigation for awhile. Just a few weeks ago in early October a separate group out of Germany published in Nature Medicine a study treating a different form of Lupus, systemic lupus erythematosus, with an anti-CD19 CART therapy. The small study in 5 participants caused complete remission of SLE symptoms on a disease activity scale at 3 months and that was maintained drug-free for up to 12 months. That by the way is complete remission of an poorly treatable life-threatening disease with a single therapeutic dose that was well tolerated. Kyverna is heading in a slightly different direction targeting lupus nephritis which specifically impacts the kidneys, but based on published data by this other group I am relatively excited about the potential here. Given, I am drawing crude analogies to non-identical therapies but on the backs of raising an $85M Series B and crafting partnerships with Intellia Therapeutics back in January, this more movement in a positive direction for Kyverna and I’m excited to see how their long-term data read out for the potential expanded use of CART therapies in autoimmune diseases. 

Closing Credits

Thanks for joining me for Life Science Today, your source for stories, insights, and trends across the life science industry. Learn more at LifeScienceTodayPodcast.com. If you like what you hear, please tell a friend. Once again, I’m Dr. Noah Goodson, I’ll see you next week. 

About the Show

Life Science Today is your source for stories, insights, and trends across the life science industry. Expect weekly highlights about new technologies, pharmaceutical mergers and acquisitions, news about the moves of venture capital and private equity, and how the stock market responds to biotech IPOs. Life Science Today also explores trends around clinical research, including the evolving patterns that determine how drugs and therapies are developed and approved. It’s news, with a dash of perspective, focused on the life science industry.