Allosteric kinase inhibitor(Allorion Therapeutics)

Pictured: Photo illustration featuring Avenzo Therapeutics CEO Athena Countouriotis/ Nicole Bean for BioSpace Having completed an oversubscribed $150 million Series A-1 funding round, Avenzo Therapeutics is looking to add at least one new cancer-focused asset in the next year, CEO Athena Countouriotis told BioSpace. The company will not be conducting in-house drug discovery, but rather licensing clinical-stage or near-clinical-stage compounds from other companies. It is a deliberate strategy undertaken by the startup, whose executives learned from their experience leading Turning Point Therapeutics, which Bristol Myers Squibb bought for $4.1 billion in 2022. Countouriotis recalled that it took Turning Point about three years from the start of discovery work to dosing of the first patient. Avenzo has an active clinical trial of an in-licensed product less than a year and a half after the company’s founding. “Rather than doing all of that inherent growth [here at Avenzo], we decided we would look for in-licensed assets,” said Countouriotis, who was president and CEO of Turning Point at the time of the BMS acquisiton. She and former Turning Point Chief Medical Officer Mohammad Hirmand started San Diego–based Avenzo in October 2022. It is a rather unique approach for a startup, Solon Moreira, assistant professor of strategy and entrepreneurship at Temple University’s Fox School of Business, told BioSpace. “You see so many smaller companies out-licensing to Big Pharma,” Moreira said. Avenzo “got our attention because that’s not as usual.” Avenzo currently has about 15 employees, more than half of whom are supporting the trial, Countouriotis said. But while the approach may be uncommon, it’s one investors appear to be on board with. Avenzo originally sought to raise $45 million in this add-on round, but the company ended up with more than triple the original goal. The First Asset In January, Avenzo paid $40 million to license a CDK2 inhibitor from Allorion Therapeutics. The deal includes an exclusive option to purchase a preclinical program with an Investigational New Drug (IND) submission planned for early 2025. The compound, now dubbed AVZO-021, is in a Phase I/II study including patients with HR+/HER2- metastatic breast cancer and other advanced solid tumors. Countouriotis told BioSpace that dosing has begun in about five patients. This trial has multiple components. AVZO-021 will be tested as a single agent and in combination with the three currently approved CDK4/6 inhibitors for breast cancer: Novartis’ Kisqali, Pfizer’s Ibrance and Eli Lilly’s Verzenio. Countouriotis said there will “likely” be a combination with an antibody-drug conjugate (ADC) before Phase I wraps up. While still in stealth mode last year, Avenzo raised nearly $197 million in its Series A round. The A-1 brought the company’s total fundraising to $347 million. With the new haul, Countouriotis expects to double the headcount to 30 in the next 12 months. “It’s going to be probably mostly R&D, and it’s going to be folks that are much more on the D than the R,” she said. Thomas Klueter, professor of entrepreneurship at IESE Business School in Barcelona, Spain, said the founders of Avenzo likely realized that their competencies were in managing clinical development rather than developing breakthrough compounds. The Turning Point–BMS connection also helped. “What were the incentives for [Allorion] to license this molecule, which was already in Phase I, to an Avenzo?” Klueter wondered. “It has to be with the credibility of the founders, which also enabled them to convince investors.” Future Plans The Series A-1 raise provides working capital for two to three years, according to Countouriotis, though the company expects to spend much of that money on a new compound within a year. She added that the goal is to strike another licensing deal in the next 12 months and a third by early 2026, both for clinical-stage assets. Avenzo also wants to go public in the next two years, Countouriotis said. Within five years, Countouriotis would like Avenzo to have enough data to bring a New Drug Application to the FDA. The company has no plans to expand beyond oncology because that has been the career focus of founders Countouriotis and Hirmand, who have collectively brought 11 cancer drugs to market, Countouriotis said. Neil Versel is the business editor at BioSpace. You can reach him at neil.versel@biospace.com. Follow him on LinkedIn or X.

Big Pharma companies continued dealmaking with Asian biotechs. The last few days of 2023 and the beginning of 2024 featured a flurry of dealmaking by the likes of AstraZeneca, Johnson & Johnson, Roche and Boehringer Ingelheim with Asian companies. Big Pharma companies are also increasingly entrusting commercialization of some products in China to domestic firms. And more. 1. AstraZeneca pays $1B to take the wheel of Gracell’s CAR-T ‘fast car’ AstraZeneca is paying $1 billion to acquire CAR-T specialist Gracell Biotechnologies in the first full buyout of an innovative Chinese biotech by a Big Pharma company. Gracell’s FasTCAR platform is designed to reduce manufacturing time and enhance T cell fitness. The company’s lead candidate, a BCMA and CD19 dual CAR-T coded GC012F has delivered some impressive early results in multiple myeloma. 2. A Christmas deal spree: See what J&J, Roche and more had in their stockings AstraZeneca picks up a friend for Tagrisso in $40M upfront deal GSK heads back to Hansoh, paying $185M upfront for another ADC Avenzo, Merck KGaA and AbbVie each ink new deals to fortify cancer pipelines A wave of cancer drug licensing deals with Asian companies were unveiled in the past few weeks. Johnson & Johnson paid $100 million upfront and promised $1.7 billion in milestones for LegoChem Biosciences’ TROP2 antibody-drug conjugate. Roche in-licensed MediLink Therapeutics’ c-MET ADC in a deal potentially worth $1 billion. Astellas penned a $1.7 billion biobuck pact for two bispecific macrophage engagers from Elpiscience Biopharma. AstraZeneca laid out $40 million in upfront and near-term milestones to take in Allorion Therapeutics’ EGFRL858R allosteric inhibitor as a potential lung cancer treatment. Allorion also out-licensed ex-Greater China rights to an early-stage CDK2 inhibitor and a preclinical asset to Avenzo Therapeutics for $40 million upfront. Just two months after buying rights to Hansoh’s B7-H4-targeted ADC, GSK has picked up a B7-H3 ADC from the Chinese biotech for $185 million upfront and up to $1.5 billion in potential milestones. 3. Boehringer bets $2B in biobucks to unlock siRNA targets for MASH treatments Outside oncology, Boehringer committed more than $2 billion in biobucks to tap Ribo Life Science’s small interfering RNA technology to treat metabolic-associated steatohepatitis, also known as nonalcoholic steatohepatitis. The Chinese biotech and its Swedish subsidiary have a platform that produces RNAi drugs that target genes specifically in liver cells. 4. 2024 forecast: Big Pharma reworks China strategy, and job cuts are part of it In the last few months of 2023, Pfizer, GSK, Sanofi and Biogen tasked local companies to commercialize some of their products in China. Increased pricing pressure and competition, especially for mature products, makes in-house commercial buildup less cost-effective for foreign pharmas, L.E.K. Consulting’s China practice leader, Justin Wang, said. The moves also come amid companies’ global cost-cutting initiatives. 5. Merck, Astellas and Pfizer bring down the house with Keytruda-Padcev FDA nod in bladder cancer The combination of Astellas and Pfizer’s Padcev and Merck’s Keytruda has won full FDA approval as a first-line treatment for bladder cancer. The go-ahead came way ahead of the FDA’s target decision date and was backed by impressive overall survival data that sparked a standing ovation when they were presented in October. The nod doubled the scope of a previous accelerated approval to now include patients who are eligible for cisplatin-based chemotherapy. 6. J&J, Legend’s Carvykti slapped with FDA black-box warning over secondary cancer risk The FDA has upgraded a warning about secondary cancers following the use of J&J and Legend Biotech’s Carvykti. The risk is now highlighted in the black box warning section of the BCMA CAR-T’s label. In the CARTITUDE-1 study, 10 of 97 Carvykti takers later developed myelodysplastic syndrome and acute myeloid leukemia. The update also comes as the FDA is investigating a new safety signal of secondary T-cell malignancies for all marketed CAR-Ts. 7. Nexletol partners Esperion and Daiichi Sankyo patch up milestone dispute with $125M settlement With a $125 million payment, Daiichi Sankyo has settled a milestone dispute with Esperion Therapeutics around the latter’s bempedoic acid products. The two companies previously clashed over a $300 million milestone payment because of different views of a cardiovascular trial’s endpoints. With the new deal, the two companies will work together to develop a triple formulation product. 8. FDA slams trio of Indian drugmakers with Form 483 filings after December inspections The FDA issued Form 483 letters to Dr. Reddy’s Labs, Torrent Pharma and Laurus Synthesis over lapses found at their plants in India. Dr. Reddy’s Bachupally R&D campus had deficient records-keeping or control procedures and lacked employee training, the FDA said. Torrent’s three-observation citation centered on its quality system. Other News of Note:  9. Olympus lung scope recall details risks of fires, internal burns 10. Takeda’s gene therapy pivot leaves JCR behind after proof-of-concept preclinical test 11. AstraZeneca, Sanofi win nod in China for RSV antibody Beyfortus 12. After issuing Form 483, FDA classifies Aurobindo plant as only needing 'voluntary' action 13. Otsuka pays $65M cash for European rights to Ionis’ phase 3 rare disease med 14. After Xiidra deal with Bausch, Novartis divests Indian eye care brands to J.B. Pharma for $116M 15. Sciwind blows into GLP-1 contention with pivotal data on Chinese rival to Novo, Lilly 16. AGC extends CDMO expansion spree, plans second manufacturing facility in Japan 17. WuXi CRDMO spinoff WuXi XDC inks partnership with IntoCell