Protein degradation therapeutics(Boehringer Ingelheim/VantAI)

Pictured: Sign with Astellas logo in front of tree/Adobe Stock, u_photo A week after licensing a novel gene therapy from Kate Therapeutics to treat X-linked myotubular myopathy, Astellas Wednesday announced a strategic collaboration with San Diego- and China-based Cullgen to develop multiple targeted protein degraders. Under the research collaboration and exclusive option agreement, the partners will jointly conduct research to identify clinical development candidates using Cullgen’s uSMITE targeted protein degradation platform featuring novel E3 ligands. Astellas is paying Cullgen $35 million upfront for access to uSMITE, which stands for ubiquitin-mediated, small molecule-induced target elimination. E3 enzymes are one of three enzyme types responsible for the specific targeting of proteins for degradation. Cullgen and Astellas plan to develop drugs that break down, as opposed to block, disease-causing proteins, according to BioPharma Dive. Following the research period, Astellas will have the exclusive option to develop and commercialize any protein degrader compounds discovered through the collaboration. Cullgen will have the opportunity to share the costs, profits and losses in the early stages of development, and to co-promote the previously identified lead program—a cell cycle protein degrader for breast cancer and other solid tumors—in the U.S. Cullgen stands to gain an additional $85 million if Astellas chooses to exercise the option for this lead program. If all milestones are achieved, Cullgen, which recently raised $35 million in a Series C financing led by AstraZeneca, could see compensation exceed $1.9 billion. In a prepared statement, Adam Pearson, chief strategy officer at Astellas, called targeted protein degradation (TPD) one of the company’s primary focuses. Masahiko Hayakawa, who heads protein degradation research at Astellas, told BioPharma Dive that the company has been investing in the drug development approach for more than a decade. Targeted protein degradation, which aims to use drugs to destroy problematic proteins, has been one of biopharma’s hottest areas in recent years. Biotech companies, including Arvinas, Kymera Therapeutics and C4 Therapeutics have sprung up expressly for this purpose, while several large biopharmas have joined Astellas on the partnering front. In April 2022, AbbVie inked an exclusive partnership with San Diego–based Plexium to develop and commercialize novel TPD therapeutics for neurological conditions. The same month, Boehringer Ingelheim announced a collaboration with VantAI to identify potential protein-degrading molecules for traditionally undruggable targets. The two are leveraging VantAI’s geometric deep learning platform to computationally streamline the design of new molecules optimized for that company’s proprietary E3 ligase platforms. Heather McKenzie is a senior editor at BioSpace, focusing on neuroscience, oncology and gene therapy. You can reach her at heather.mckenzie@biospace.com. Follow her on LinkedIn and Twitter @chicat08.

Kymera Therapeutics has raised $150 million through the sale of more than 2,769,000 shares of common stock that will support the company's ongoing clinical and preclinical programs. Kymera, which is focused on the field of targeted protein degradation, said the financing will be used to support its ongoing research and development programs, as well as for general corporate purposes. The company has three programs in the clinic that target IRAK4, IRAKIMiD, and STAT3, which are within the IL-1R/TLR or JAK/STAT pathways. One of those programs, KT-333, a first-in-class degrader of the transcriptional regulator STAT3 that is being assessed in a Phase I trial for the treatment of Peripheral T-cell Lymphoma, received Orphan Drug designation from the FDA in June. STAT3 activation is understood to be a key modulator for PTCL, and there are currently no approved therapies for the disease that target this pathway. Kymera's other Phase I asset, KT-413, targets the degradation of both IRAK4 and IMiD substrates Ikaros and Aiolos. According to the company, the drug is expected to broaden activity against MYD88-mutant Diffuse large B-cell lymphoma (DLBCL). In June, the company dosed its first patients in the Phase I studies of KT-333 and KT-413. Both trials will assess the pharmacology and safety of these first-in-class investigational medicines. In addition to the oncology-targeted assets, Kymera's KT-474 targets IRAK4, a protein known to play a significant role in inflammation mediated by toll-like and IL-1 receptors. IRAK4 plays a role in diseases such as rheumatoid arthritis, atopic dermatitis and hidradenitis suppurativa, a condition that causes painful lumps to form under the skin. In partnership with pharma giant Sanofi, Kymera is advancing its IRAK4 degrader program in various autoinflammatory and autoimmune diseases and in precision-medicine targeted oncology indications. In in vitro and in vivo tests, KT-474 demonstrated potent anti-inflammatory activity. Nello Mainolfi, president and chief executive officer of Kymera, told BioSpace that the financing was an unsolicited offer. This morning, Mainolfi said investors in the company have been supportive of its vision and protein degradation program. Protein degradation has become a hot space for companies to pour funding. Over the past several months, multiple partnerships have been forged at billions of dollars in this space. Some of the deals include a partnership between Germany's Boehringer Ingelheim and Roivant Sciences company VantAI. AbbVie and Plexium forged a deal to develop TPDs for neurological conditions. VantAI also entered into protein degradation partnerships with Janssen and BluePrint Medicines. Bristol Myers Squibb has also struck a multi-billion deal with Evotec in this space. Mainolfi touted the potential of protein degradation, calling it the most impactful of all modalities for treating disease. He pointed to successes in gene therapy, RNA-based therapies and other modalities and said they have all changed the face of medicine, "but none of them have the potential to impact the way protein degradation does." "Targeted protein degradation has a huge impact on patients across multiple diseases," he said. "It offers broad potential to go after a new class of targets, and it's not surprising that more companies are being founded on new takes in the space." Kymera uses its Pegasus platform to develop its protein degraders. The platform is designed to help cells target proteins found on them that could be detrimental and accelerate disease development. According to the company, the Pegasus platform is able to hijack and redirect the ubiquitin-proteosome system," which is essential to regulating cellular process and natural protein degradation. Mainolfi said the financing, which will bring the company's cash and cash equivalents to about $600 million, will allow the company to continue to invest in its pipeline without extending its cash runway. Before the investment, the company had enough cash on hand to support operations through 2025, but now, they will be able to push beyond that with the latest financing support. Mainolfi, a co-founder of the company, noted that the funding will not only support the ongoing clinical development of its three Phase I assets but also support the potential progression of developmental assets toward clinical studies. He anticipates that the company will be able to drive at least one developmental program into the clinic every year over the next five years. The Watertown, Mass.-based company sold the shares at $26 per share and investors in the private investment round will have an option to acquire up to an aggregate 3 million shares of additional common stock. The investors in the financing include a non-disclosed healthcare-focused fund based in the United States, the Biotechnology Value Fund, as well as Avoro Capital Advisors, EcoR1 Capital, Rock Springs Capital and Redmile Group. Kymera's stock closed at $29.09 on Thursday.