Loxo Oncology, Inc.

Eli Lilly has turned to a biotechnology startup for help building its pipeline of cancer drugs, agreeing on Monday to purchase an experimental cancer drug from privately held Scorpion Therapeutics for as much as $2.5 billion.As part of the deal, Scorpion will spin out a new, independent company that will hold its other assets as well as inherit its employees. Lilly will take a minority stake in the new company, which will be owned by Scorpions current shareholders, among them Atlas Venture, Vida Ventures and Omega Funds.Current Scorpion CEO Adam Friedman will lead the new company along with other members of the startups management.The acquisition hands Lilly a medicine, dubbed STX-678, that is aimed at tumors driven to growth by mutations to a gene called PI3Ka. So-called PI3Ka mutations are among the most common drivers of cancer, affecting more than 160,000 people diagnosed each year with breast, gynecological and head and neck cancers in the U.S., according to Scorpion.A handful of medicines already available, like Novartis Piqray and AstraZenecas Truqap, as well as others in clinical development also target PI3Ka mutations.Scorpion has claimed its drug could be more selective and potent than existing PI3Ka inhibitors, which block normal, or wild-type, PI3Ka and as a result are tough to tolerate. Existing drugs also dont readily reach the brain tissue into which many solid tumors spread. Scorpion says its drug might overcome these limitations and has advanced the treatment into a Phase 1/2 trial in multiple tumor types, among them a common form of breast cancer.Scorpion has been collaborating with Pfizer to study STX-678 together with a so-called CDK4 inhibitor. Lilly sells a drug, called Verzenio, that similarly targets CDK4 alongside a related protein.The deal will expand a cancer drug division Lilly has poured considerable resources into as a complement to its lucrative metabolic disease business. Lilly acquired Loxo Oncology in 2019 and, since then, has used deals to buy into other areas of precision oncology such as radiopharmaceuticals and antibody-drug conjugates.Verzenio, which Lilly discovered and developed internally, has become the top-selling drug of its class, though much of Lillys revenue is derived from its diabetes and weight loss treatments. Lilly also has in its pipeline an internally developed PI3Ka inhibitor thats in Phase 1 testing.Lillys deal with Scorpion adds to an upward trend in private biotech M&A. The increase has coincided with a weakening market for initial public offerings, which as forced many mature startups to explore strategic options.Scorpion was co-founded in 2020 by Gary Glick, who helped the company raise nearly $300 million in venture funding before departingin 2021. Prior to Scorpion, Glick led Lycera, which inked a 2015 deal with Celgene, and IFM Therapeutics, which has spun off multiple companies that were acquired by Bristol Myers Squibb and Novartis.Glicks latest company, Odyssey Therapeutics, is developing treatments for inflammatory diseases. '

On December 16, Innovent Biologics and Eli Lilly announced a collaboration agreement for the non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor, pirtobrutinib, in mainland China. Under this agreement, Innovent Biologics will handle the import, sales, promotion, and distribution, while Eli Lilly will manage R&D and post-market medical affairs. On October 29, Eli Lilly’s pirtobrutinib received approval from the National Medical Products Administration (NMPA) for treating relapsed or refractory mantle cell lymphoma (MCL) in adults who have previously received BTK inhibitor treatments. Currently, the domestic market has five approved BTK inhibitors, including ibrutinib, zanubrutinib, ocatabrutinib, and acabrutinib. Sanofi’s Tolebrutinib and Rilzabrutinib are in Phase III clinical trials, while CT-1530 from Shouyao Holdings is in Phase II. The robust development of BTK inhibitors indicates potential market changes. BTK inhibitors work by targeting the BCR signaling pathway, binding to BTK, inhibiting its phosphorylation, and inducing apoptosis, effectively managing B-cell malignancies. Before BTK inhibitors, lymphoma treatments were limited to chemotherapy, anti-CD20 antibodies, and radiotherapy. Ibrutinib, the first BTK inhibitor, revolutionized B-cell cancer treatment since its 2013 debut and was approved in China in 2017. However, sales of ibrutinib have slowed due to competition from similar drugs. Zanubrutinib, developed by BeiGene, reached $1.297 billion in global sales in 2023, marking the first domestic drug to achieve such success, but it now faces increasing competition. Pirtobrutinib, as the first and only non-covalent BTK inhibitor, intensifies competition in this niche market. It shows potential to overcome resistance to covalent BTK inhibitors and offers a new option for relapsed/refractory MCL patients. To highlight its efficacy, Eli Lilly conducted a head-to-head study in the BRUIN MCL-321 trial. By 2030, pirtobrutinib is projected to capture 60% of the chronic lymphocytic leukemia market, equating to $3 billion in annual sales. With advancing technology and new drug development, the BTK market is expanding rapidly. According to Frost & Sullivan, the global BTK market could reach $20 billion by 2025 and $26.1 billion by 2030. In China, the market size is expected to reach RMB 13.1 billion by 2025 and RMB 22.5 billion by 2030. The growing BTK market has attracted numerous pharmaceutical companies. At least 20 BTK inhibitors are in clinical trials domestically, with Shouyao Holdings, Hengrui Medicine, and Hezheng Pharmaceutical leading the way. Ibrutinib’s core patent will expire on December 28, 2026, and at least 10 companies are preparing generics. This will lead to fierce competition among original drugs, domestic innovations, and generics. BeiGene’s zanubrutinib remains a key product, but new competitors like pirtobrutinib pose challenges. The success of pirtobrutinib in China’s market is worth monitoring. Originally developed by Redx Pharma and acquired by Loxo Oncology, pirtobrutinib was purchased by Eli Lilly for $8 billion in 2019. In March 2022, Innovent Biologics secured Chinese commercialization rights for pirtobrutinib with an initial payment of $45 million. The partnership between Innovent Biologics and Eli Lilly began in 2015 and has expanded through multiple projects. Despite setbacks like sintilimab’s rejection by the U.S. FDA in 2022, their collaboration continues with other initiatives. Their 2019 cooperation on IBI362, a dual GLP-1R and GCGR agonist, is in Phase II/III trials for Type 2 diabetes and weight loss. In March 2022, Eli Lilly’s ramucirumab was approved in China, granting Innovent Biologics exclusive commercialization rights. Additionally, they collaborate on selpercatinib, a RET inhibitor for gene fusion tumors. The cooperation and competition between domestic and multinational pharmaceutical companies are becoming a norm. This model offers a win-win strategy for navigating the global market.

What drugs have been approved this week?1. Novartis: FDA Approves New First-Line Indication for Bcr-Abl Inhibitor On October 29, Novartis announced that the FDA has granted accelerated approval for a new indication for Scemblix (Asciminib) to treat newly diagnosed adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP). Previously, in October 2021, Scemblix was approved in the U.S. for adult patients with Ph+ CML-CP who have undergone at least two tyrosine kinase inhibitor (TKI) treatments or possess the T315I mutation. The drug later received approval in Japan and the European Union in March and August 2022, respectively. According to the press release, expanding the treatment line is expected to increase the eligible patient population by approximately fourfold. Scemblix is a STAMP inhibitor developed by Novartis that specifically targets the myristoyl pocket of the BCR-ABL1 protein. The accelerated approval was based on results from the Phase III ASC4FIRST clinical trial, which measured major molecular response (MMR) at week 48. This study compared once-daily Scemblix with standard TKI therapies selected by the investigators (Imatinib, Nilotinib, Dasatinib, or Bosutinib). Results demonstrated that Scemblix improved MMR rates at week 48 by nearly 20% compared to the standard TKI therapies (68% vs. 49%, p<0.001) and by nearly 30% compared to Imatinib monotherapy (69% vs. 40%, p<0.001). 2. CStone Pharmaceuticals: PD-L1 Inhibitor Approved in the UK On October 31, CStone Pharmaceuticals announced that the UK’s MHRA approved Sugemalimab, a PD-L1 inhibitor, in combination with platinum-based chemotherapy for first-line treatment of metastatic NSCLC in adults without EGFR-sensitizing mutations or ALK, ROS1, or RET genomic alterations. Sugemalimab was previously approved by the European Commission in July this year. The latest approval is based on findings from the Phase III GEMSTONE-302 trial, a multicenter, randomized, double-blind clinical study evaluating the efficacy and safety of Sugemalimab combined with platinum-based chemotherapy versus placebo with platinum-based chemotherapy in stage IV NSCLC patients. The primary endpoint was progression-free survival (PFS) assessed by investigators. 3. Eli Lilly: Non-Covalent BTK Inhibitor Approved in China On October 29, China’s NMPA announced the approval of Eli Lilly’s Pirtobrutinib tablets for adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have previously received a Bruton’s tyrosine kinase (BTK) inhibitor. Pirtobrutinib is a highly selective, reversible oral BTK inhibitor that interacts with water molecules and BTK residues near the ATP binding site, rather than binding to the C481 site, demonstrating potential to overcome resistance to covalent BTK inhibitors. It inhibits both wild-type and C481-mutant BTK. Originally developed by Redx Pharma, Pirtobrutinib was acquired by Loxo Oncology in July 2017. In January 2019, Eli Lilly acquired Loxo Oncology for $8 billion, securing rights to the drug. In March 2022, Innovent Biologics obtained a priority negotiation right to commercialize Pirtobrutinib in China with an initial payment of $45 million. 4. Hengrui Pharmaceutical: New Indication Approved for Vunakizumab in Ankylosing Spondylitis On October 29, Hengrui’s Vunakizumab injection was approved in China for a new indication to treat ankylosing spondylitis. Previously, on August 27, Vunakizumab was approved for adult patients with moderate-to-severe plaque psoriasis suitable for systemic therapy or phototherapy, marking this as the second approved indication. Vunakizumab is an IL-17A-targeting humanized IgG1 monoclonal antibody developed by Hengrui with 0.8% murine components to increase IL-17A affinity while reducing immunogenicity. Compared to already approved Secukinumab and Ixekizumab, Vunakizumab exhibits higher IL-17A affinity and stronger inhibition of IL-17A/IL-17R interaction. What major clinical trial results were released this week?1. Novo Nordisk: Semaglutide Phase III Trial for MASH Successful, Regulatory Submission Planned On November 1, Novo Nordisk reported promising primary results from Part 1 of its ongoing ESSENCE trial. Findings showed semaglutide led to significant improvement in liver fibrosis and alleviation of metabolic dysfunction-associated steatohepatitis (MASH) symptoms. Novo Nordisk plans to submit regulatory applications in the U.S. and Europe in early 2025 for this indication. Detailed results from the ESSENCE study will be presented at a medical conference in 2024, while Part 2 of the study will continue through 2029. The ESSENCE study is a 240-week, Phase III double-blind clinical trial evaluating the efficacy of a weekly subcutaneous injection of 2.4 mg semaglutide in adults with advanced liver fibrosis (stage 2 or 3) due to MASH. At week 72, 37% of semaglutide-treated patients achieved liver fibrosis improvement, compared to 22.5% in the placebo group, and 62.9% of patients showed MASH resolution, versus 34.1% in the placebo group. 2. Eli Lilly: Donanemab Modified Dose Successful in Phase 3b Alzheimer’s Disease Trial On October 29, Eli Lilly shared positive results from its Phase 3b TRAILBLAZER-ALZ 6 study. The study, conducted on early Alzheimer’s disease (AD) patients, met its primary endpoint by significantly reducing ARIA-E symptoms by week 24. TRAILBLAZER-ALZ 6 is a randomized, double-blind, global study that explored the incidence of amyloid-related imaging abnormalities (ARIA-E) and amyloid clearance across four adjusted dosing regimens of donanemab in early AD patients. Results showed a 41% reduction in ARIA-E risk with the adjusted regimen (14%) compared to the standard dosing (24%). The adjusted regimen was particularly effective in APOE4 homozygous patients, reducing ARIA-E occurrence by 67% (19% versus 57%). 3. BMS Presents CAR-T Therapy Data for Systemic Lupus Erythematosus Bristol-Myers Squibb will present the initial clinical outcomes of its investigational CD19-targeted CAR-T therapy, CC-97540, at the ACR conference. The study (NCT05869955) included nine patients with severe, refractory autoimmune diseases as of June 2024, with four SLE patients showing kidney involvement that had not responded to previous treatments. The study reported a mild (Grade 1) cytokine release syndrome in one patient, which resolved within a day without cytokine or corticosteroid intervention. Additionally, three out of four patients (75%) experienced transient lymphopenia, a typical side effect, with no neurotoxicity or serious adverse events observed. 4. Akeso Biopharma: Full Phase III Data for AK111 in Plaque Psoriasis Released On October 28, Akeso Biopharma announced favorable long-term efficacy and safety results from its AK111-301 Phase III trial of gumokizumab (AK111) for moderate-to-severe plaque psoriasis. Gumokizumab is a humanized IgG1 monoclonal antibody targeting IL-17A, developed to bind to human IL-17A with high specificity and affinity to inhibit psoriasis-associated signaling pathways. The study followed patients for up to 56 weeks, with findings showing that gumokizumab demonstrated excellent long-term efficacy and a high response rate, providing a promising new treatment option for psoriasis patients. 5. Ji Xing Pharmaceuticals: Successful Phase III Trial of LNZ100 for Presbyopia in China On October 28, Ji Xing Pharmaceuticals and LENZ Therapeutics announced top-line results from the Phase III JX07001 trial of LNZ100 for presbyopia in China. LNZ100 met its primary and key secondary endpoints, significantly improving near visual acuity (BCDVA) with sustained distance vision for up to 10 hours post-dose in presbyopic patients. Approximately 84% of participants saw a two-line improvement in near vision, while 69% experienced a three-line improvement within 30 minutes of dosing. At three hours, these improvements were observed in 88% and 74% of patients, respectively, with no severe treatment-related adverse events reported, suggesting LNZ100’s good tolerability. For more information on the progress of drug development, please consult the Synapse database.