Alice Matthews and Adrian Toutoungi dig through the stand-out July 2024 biopharma deals. Neurodegenerative disease deals are resurgent, after a few months dominated by other therapeutic indications (and in the month that the CHMP gave a negative opinion for Biogen/Eisei's Lequembi™). Other themes for the month included: (i) continued interest in discovery stage deals for antibody-drug conjugates (ADC), following on from our June 2024 update; and (ii) a cold wind blowing in the SHP2 inhibitor space; (iii) headwinds for AIDD-focused deals.

Deal of the month

• Roche has invested an upfront payment of $50 million in upfront and near-term milestone payments for an exclusive license to a Sangamo Therapeutics' proprietary zinc finger repressor directed at the tau gene (and at a second neurology target which has not yet been disclosed), with a view to developing it into an IV-administered (i.e. in vivo) genomic medicine. Tau protein is important to brain health but can sometimes form toxic clumps which damage neurons. Many scientists believe that tau protein is a key driver of neurodegenerative diseases such as Alzheimer's. In addition, Sangamo could receive up to $1.9 billion in development and commercial milestone payments, as well as tiered royalties on net sales. The California-based biotech has also agreed to exclusively license to Roche, for tau and the second neurology target, its proprietary, neurotropic adeno-associated virus (AAV) capsid, STAC-BBB, which has demonstrated potent blood-brain barrier penetration and brain transduction in nonhuman primates.
• Anti-amyloid antibodies have dominated the therapeutic space for AD (Biogen's aducanemab, Biogen/Eisei's lecanemab, Lilly's donanemab) for the last 2-3 years. This pre-clinical deal indicates that the tau hypothesis (i.e. that the development of Alzheimer's disease is primarily driven by abnormalities in the tau protein, rather than by amyloid-beta (Aβ) plaques) is still very much alive.
• CRISPR-mediated gene editing, base editing and prime editing have dominated discussion in the genomic medicine space over recent years, not least since Vertex/CRISPR obtained FDA approval for Casgevy™ 8 months ago. This deal is a useful reminder that other gene editing technologies (such as Sangamo's zinc finger nucleases, and TALENS) exist (though the zinc finger protein here is coupled with a repressor, not a nuclease, so strictly speaking this is not a gene editing medicine). 

Other July biopharma deals which caught our eye included:

• Also in CNS/neurodegeneration, Biogen has announced a discovery stage collaboration with two diagnostics developers, Beckman Coulter and Fujirebio. The purpose of this collaboration is to identify blood-based biomarkers that reflect the presence of diseased tau in the brain, and potentially to clinically advance and commercialise tests for such biomarkers. Biogen will provide Alzheimer's disease clinical study data and expertise in biomarker research, while Beckman Coulter and Fujirebio will provide the development, manufacturing and commercialisation of diagnostics. The financials of this partnering deal have not been disclosed. Earlier this year, Biogen announced plans to develop the development of an experimental, tau-targeting therapy (BIIBo80), which explains Biogen's interest in the parallel development of a tau diagnostic test.
• Roche has terminated its cancer drug license and collaboration agreement with Relay Therapeutics, initially aimed at the development and commercialisation of RLY-1971 (now known as migoprotafib or GDC-1971), an experimental SHP2 inhibitor. The agreement was entered into in 2020 and involved an upfront payment to Relay of $75 million. Had the collaboration have been successful, Relay stood to gain an additional $25 million of near-term payments, and either $695 million in additional development, commercialization and sales-based milestones and low-to-mid teen royalties on global net sales (or, if it exercised an option to opt into a 50:50 cost/US profit share, $410 million of ex-US milestones). This termination follows AbbVie's termination of its collaboration with Jacobio Pharmaceuticals on SHP2 inhibitors in July 2023, and also Sanofi's walking away from its licensing deal with Revolution Medicines to develop SHP2-targeting treatments for cancer. In the same month in which Exscientia and Recursion merged, widely seen by the market as a defensive manoeuvre by two of the leading publicly-traded AIDD companies, news of this collaboration termination comes as another setback for AIDD.
• Ideaya Biosciences (South San Francisco) has entered into an option and licence agreement with Biocytogen Pharmaceuticals (Beijing)  for the potential first-in class B7H3/PTK7 topo-I-payload bispecific antibody drug conjugate (BsADC) program. B7H3/PTK7 has been found to be co-expressed in multiple solid tumour types, including lung, colorectal, head and neck cancers. In return for granting Ideaya an option for an exclusive worldwide licence to the pre-clinical program, Biocytogen will receive an upfront fee, option exercise and milestone payments totalling up to $406.5 million, including development and regulatory milestones of $100 million. In other news, Biocytogen has also entered into an option and licence agreement with SOTIO Biotech, where Biocytogen has granted SOTIO the option to license multiple fully human bispecific antibodies generated with Biocytogen’s proprietary RenLite® platform, which SOTIO will use to develop next-generation ADCs targeting solid tumours. Biocytogen is eligible to receive upfront and potential milestone payments of up to $325.5 million, and low single-digit royalties on net sales. Currently there are no approved BsADC therapeutics, but ten (10) BsADCs are in clinical trials. They are thought to provide certain advantages compared to traditional ADCs (15 approved; 140 in clinical trials), particularly for solid tumours, and could emerge as important part of next gen ADC technologies.
• Vertex Pharmaceuticals has entered into a research collaboration agreement with Orum Therapeutics (South Korea), for an exclusive, worldwide licence to its degrader-antibody conjugate (DAC) technology in relation to three targets. Orum will receive $15 million upfront, plus up to $310 million per target in milestone payments and royalties on future sales. Orum's technology is similar to an ADC (discussed above), but rather than pairing a toxin with a targeting antibody, it replaces the toxin with a protein-degrading compound. Eliminating the right cellular protein(s) will lead to cell death. Vertex will be responsible for all research, development and commercialization efforts as part of the deal. This early-stage research collaboration aims to develop a different kind of conditioning regimen for more intense therapies (such as Vertex' sickle-cell disease gene editing therapeutic, Casgevy™) than the chemotherapies currently used.