Affimed(US:AFMD)2019-03-27 11:01Product Development - The company is focused on developing highly targeted cancer immunotherapies using its proprietary ROCK® platform, which enables the creation of next-generation bispecific antibodies [282]. - The lead product candidate, AFM13, is designed to engage innate immune cells and has shown a 1,000-fold higher affinity for CD16A compared to native antibodies, targeting relapsed/refractory Hodgkin lymphoma and CD30-positive lymphoma patients [298]. - The company has established a clinical pipeline with five programs, three of which retain global commercial rights, focusing on orphan or high-medical need indications [285]. - AFM11, another lead product candidate, has shown promising results in preclinical studies and has treated 33 patients across two clinical Phase 1 studies for relapsed/refractory non-Hodgkin lymphoma and acute lymphocytic leukemia [299]. - AFM24 completed a toxicology study in cynomolgus monkeys at doses up to 75 mg/kg with no observed toxicities, contrasting with significant toxicity seen in Cetuximab [319]. - AFM13 achieved an objective response rate (ORR) of 88% in a phase 1b study, with complete metabolic responses in 46% of patients [312]. - AFM13 demonstrated tumor shrinkage or slowing of tumor growth in 16 of 26 patients eligible for efficacy evaluation, with complete remissions in 3 of 11 patients treated in the highest dose cohorts [308]. - The company is conducting two phase 1 clinical studies of AFM11, with a total of 33 patients treated across both studies [318]. - AFM13 is being investigated in combination with Merck's anti-PD-1 antibody Keytruda, with a focus on enhancing therapeutic efficacy [314]. - The phase 1b clinical study of AFM13 in combination with Keytruda® showed an overall response rate (ORR) of 88% in 24 patients, with complete metabolic responses in 46% and partial metabolic responses in 42% [378]. - The phase 1 clinical study of AFM13 enrolled 28 patients, with a median of six prior lines of therapy, and demonstrated anti-tumor activity at doses of 1.5 mg/kg and above, achieving an overall response rate of 23% in a subgroup [383][385]. - AFM13 treatment resulted in a dose-proportional increase in systemic exposure, with a mean half-life of 9-19 hours for the 1.5 mg/kg cohort, and was detectable in peripheral blood up to 168 hours post-infusion [389]. - The company plans to initiate a phase 2b study for AFM13 in relapsed/refractory Hodgkin Lymphoma, which could support an application for registration based on high medical need [392][393]. - AFM13 demonstrated a favorable safety profile, with less than 30% of adverse events classified as severe, primarily consisting of mild to moderate fever and chills [384]. Collaborations and Partnerships - Collaborations with organizations like the Leukemia and Lymphoma Society and Merck aim to expedite development and patient enrollment for AFM13 [294]. - The collaboration with MD Anderson aims to evaluate AFM13 in combination with cord-blood derived NK cells, with plans for a clinical study in relapsed/refractory CD30-positive lymphoma patients [398]. - The collaboration with Genentech resulted in an initial payment of $96 million and potential milestone payments totaling approximately $5.0 billion, including $250 million for development activities [418][421]. - Genentech is responsible for the majority of research, development, and commercialization costs for the licensed product candidates under the collaboration agreement [422]. - The Leukemia & Lymphoma Society (LLS) agreed to co-fund the clinical development of AFM13 with contributions up to approximately $4.4 million, of which $4.2 million has already been received [437]. - The research funding agreement with LLS was amended to prioritize the development of AFM13 as a combination therapy following a collaboration with Merck [437]. Market and Competitive Landscape - The biopharmaceutical industry is characterized by intense competition, with many companies developing therapies for cancer disorders, including major pharmaceutical and biotechnology firms [471]. - The company faces potential competition from established therapies and new entrants, which may impact its market position and commercial opportunities [479]. - There are approximately 9,000 new cases of Hodgkin Lymphoma (HL) in the United States annually, with about 4,000-5,000 patients being refractory to or relapsing from standard therapy [351][352]. - Approximately 6,000 to 8,000 relapsed/refractory cancer cases per year in North America, the European Union, and Japan are attributed to CD30+ hematological malignancies [355]. - The total annual incidence of all B cell lymphoma subtypes in North America, the European Union, and Japan is about 160,000 cases, with DLBCL alone representing about 46,000 new patients annually [357]. Financial and Funding - The company received a €2.4 million ($3 million) grant from the German Federal Ministry of Education and Research, covering approximately 40% of funding for a multi-specific antibody development program [350]. - The agreement with Amphivena included milestone payments totaling €7.5 million, with the first three milestones successfully reached [427]. - As of December 31, 2018, the company had invested a total of $4.0 million in Amphivena, owning approximately 7% of its outstanding equity [428]. - Amphivena received €14.5 million in payments for research and development services under the license and development agreement, which has now expired [429]. Intellectual Property - The company has developed a strong patent portfolio in bispecific antibody therapeutics, supporting both internal development and potential out-licensing opportunities [305]. - The patent portfolio for AFM13 includes three families, with the first patent family expiring in 2019 and the second in 2020 [451][452]. - The patent portfolio for AFM11 includes one family granted in multiple countries, with patents expiring in 2019 and others expiring in 2030 or 2031 [453]. - The patent portfolio for AFM24 includes patents on the TandAb format, with some patents expiring in 2026 [454]. - The immune cell engager platform patent portfolio includes patents expiring in 2019 and 2030, covering various therapeutic uses for viral, bacterial, and tumoral diseases [456]. - Patent applications for trispecific antibody formats were submitted in 2015 and 2016 across multiple countries, indicating ongoing development in this area [457]. - The company has out-licensed patents covering the BCMA/CD16A compound, which includes a granted patent family similar to other TandAb formats [455]. - Exclusive and non-exclusive patent and know-how license agreements have been established, which include obligations for development milestones and sales royalties [459]. - The FDA allows for patent term extensions of up to five years for approved drugs, which the company plans to pursue for its products upon receiving approval [460]. Company Operations - The company employs 69 personnel at its main offices in Heidelberg, with approximately 60% holding advanced academic degrees [288]. - The company aims to leverage its technology platforms to continue building its cancer immunotherapy pipeline and enhance its intellectual property portfolio [293]. - The company plans to build a commercial sales force in the U.S. and Europe to market its product candidates upon regulatory approval [286]. - A focused sales and marketing organization will be built prior to receiving marketing approvals to effectively target oncologists [469]. - The company relies on contract manufacturing organizations (CMOs) for drug substance and product, ensuring compliance with Good Manufacturing Practice (GMP) regulations [466]. - The AFM13 manufacturing process has been successfully scaled to meet clinical demands, with ongoing efforts to establish commercial-scale production [467]. Clinical Insights - The management team has extensive experience in the biopharmaceutical industry, contributing to the development and commercialization of several approved drugs [304]. - Cancer immunotherapy is increasingly significant, with various approaches including vaccinations and checkpoint modulators being explored [334]. - The projected medical costs associated with cancer reached $125 billion in 2010, expected to increase by 27% to at least $158 billion by 2020 [330]. - The 5-year relative survival rate for all cancers diagnosed from 2008-2014 was 69% [330]. - Adcetris® treatment in relapsed/refractory Hodgkin lymphoma (HL) patients resulted in an overall response rate of 75% and a complete response rate of 34% [354]. - The median progression-free survival after Adcetris® is only 9.3 months, with considerable adverse events like neutropenia and neuropathy [354]. - Nivolumab and pembrolizumab show overall response rates of 64% to 74% in relapsed/refractory classical HL patients post-brentuximab vedotin, with complete remission rates of 12% to 25% [355]. - The pivotal "TOWER" study showed that 76% of patients treated with blinatumomab achieved complete remission and were MRD negative, compared to 48% for chemotherapy [402]. - AFM11 demonstrated a 100-fold higher affinity to the CD3 receptor than a reference BiTE molecule, maintaining cytotoxic potency even at lower effector cell to tumor cell ratios [403]. - The company’s immune cell engagers bind to immune cells with approximately 1,000-fold higher affinity than IgG-based antibodies, enhancing the activity of innate immune cells [343]. - The company’s T cell engager lead candidate AFM11 binds to CD3 and CD19, demonstrating target-dependent cytotoxicity at low picomolar concentrations [348]. - AFM13 is a first-in-class innate cell engager targeting CD30, showing higher cytotoxic potency than native anti-CD30 antibodies [372]. - AFM13 has been granted orphan drug status for the treatment of HL in the United States and the European Union [377]. - The clinical development of AFM13 includes a revised study design to adapt to the availability of anti-PD-1 antibodies, focusing on heavily pretreated patient populations [377].