Curis(US:CRIS)2019-03-26 21:04Drug Development and Clinical Trials - Fimepinostat has shown an objective response rate (ORR) of 23% in MYC-altered patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) based on combined results from Phase 1 and interim Phase 2 studies[29]. - The median duration of response for MYC-altered patients treated with Fimepinostat is 13.6 months, compared to 8.8 months for MYC-negative patients[29]. - CA-4948 is currently undergoing a dose escalating clinical trial in patients with non-Hodgkin lymphomas, with initial Phase 1 clinical data expected in mid-2019[35]. - CA-170 is being developed to selectively target VISTA and PDL1 immune checkpoint proteins, demonstrating anti-tumor activity in syngeneic mouse tumor models[37]. - Curis plans to initiate a Phase 1 combination study with venetoclax in DLBCL patients with MYC and BCL2 gene alterations in the first half of 2019, with initial data expected in the second half of 2019[32]. - The clinical development of Fimepinostat began in January 2013, with a recommended dose of 60 mg administered orally once daily[26]. - CA-170 demonstrated a dose proportional and predictable PK profile, with a significant increase in circulating CD8+ T cells expressing activation markers within 24 hours of oral dosing[40]. - Multiple patients experienced tumor shrinkages, including two with non-small cell lung cancer and one with Hodgkin lymphoma[40]. - Enrollment of mesothelioma patients for the CA-170 study began in January 2019, with initial clinical data expected in the second half of 2019[41]. - CA-327, an oral small molecule drug candidate, targets PDL1 and TIM3 immune checkpoint proteins and has shown anti-tumor activity in mouse models[43]. Financials and Revenue - Curis has received milestone and royalty payments from Genentech totaling $10.4 million in 2018, accounting for 100% of its revenue, all related to the commercialization of Erivedge[23]. - Curis is eligible to receive up to $115.0 million in contingent cash milestone payments related to the development of Erivedge, of which $59.0 million has been received to date[71]. - Curis Royalty is entitled to a royalty on net sales of Erivedge ranging from 5% to 7.5%, with a potential 2% reduction in certain circumstances due to competition[72]. - In Q3 2015, Genentech reduced royalties to Curis Royalty on Erivedge net sales in the U.S. by 2% following the approval of a competing product, Odomzo®[74]. - Curis Royalty received a $30.0 million loan at an annual interest rate of 12.25% to finance operations, secured by royalty payments from Genentech[77]. - A new credit agreement with HealthCare Royalty Partners was established in March 2017, providing a $45.0 million loan to refinance previous obligations[79]. - The Oberland Purchase Agreement resulted in Curis Royalty receiving an upfront purchase price of $65.0 million, with $27.5 million in net proceeds after transaction costs[81]. - Curis Royalty will receive milestone payments of $17.2 million and $53.5 million based on future royalty payments exceeding specified thresholds[81]. Collaboration and Licensing - The company has licensed four programs under its collaboration with Aurigene, focusing on immuno-oncology and precision oncology[19]. - The collaboration with Aurigene includes licensing four programs, with remaining unpaid obligations of $42.5 million per program related to regulatory approval and commercial sales milestones[53]. - The company has paid $14.5 million in research payments and waived $19.5 million in milestones under the collaboration agreement with Aurigene[53]. - Tiered royalties on annual net sales of products to Aurigene range from high single digits up to 10%[54]. - The collaboration agreement allows for termination by either party for uncured material breach, with specific conditions for program-related breaches[60]. - The company issued 3,424,026 shares valued at $24.3 million to Aurigene as part of the collaboration agreement[48]. - The collaboration agreement with Genentech may be terminated by either party with prior notice, affecting the rights to royalties and milestone payments[76]. - The collaboration agreement with Genentech allows for sublicensing and covers molecules inhibiting the Hedgehog signaling pathway for therapeutic applications[70]. Intellectual Property - As of December 31, 2018, the company holds 80 issued or allowed U.S. patents expiring between 2019 and 2036, with numerous pending patent applications[87]. - The company has 28 issued U.S. patents related to fimepinostat, expiring between 2027 and 2032, including the composition of matter patent expiring in 2032[88]. - The company has obtained exclusive licenses to Aurigene's intellectual property for various immuno-oncology programs, with ten issued or allowed U.S. patents included in the portfolio as of December 31, 2018[89]. - The company has 36 issued or allowed U.S. patents related to the Hedgehog signaling pathway, including patents covering Erivedge's composition of matter, which expires in 2028[90]. Regulatory Environment - The company is subject to extensive government regulations regarding the research, development, and approval of pharmaceutical products, requiring substantial time and financial resources[97]. - The FDA requires a 30-day waiting period after filing an IND before clinical trials can begin, allowing for review of potential health risks[105]. - The company must conduct preclinical studies to evaluate product chemistry, toxicity, and formulation before testing in humans[102]. - The company must submit information about clinical trials to the NIH for public dissemination on ClinicalTrials.gov[111]. - The FDA requires sponsors of investigational drugs for serious diseases to publicly disclose their policies for expanded access, effective upon the initiation of Phase 2 or Phase 3 studies, or within 15 days of receiving breakthrough therapy designation[114]. - The application user fee for submitting a New Drug Application (NDA) requiring clinical data is $2.6 million for the federal fiscal year 2019, with an annual program fee of $0.3 million for approved NDAs[122]. - The FDA aims to complete a preliminary review of an NDA within 60 days and strives for substantive review within ten months, or six months for priority review products[123][132]. - The FDA may grant accelerated approval for products that provide meaningful therapeutic advantages based on surrogate endpoints that predict clinical benefit, particularly in long disease courses like cancer[134]. - The FDA may designate products for Fast Track, Breakthrough Therapy, Priority Review, and Regenerative Advanced Therapy to expedite the review process for serious conditions[127][131][132][133]. - Clinical trials are conducted in four phases, with Phase 3 being pivotal for FDA approval, requiring extensive data from a larger patient population[118]. - Sponsors must submit progress reports detailing clinical trial results at least annually, with IND safety reports required for serious adverse events[119]. - The FDA may require a Risk Evaluation and Mitigation Strategy (REMS) to ensure that the benefits of a product outweigh its risks, which can impact market potential[125]. - The FDA conducts pre-approval inspections of manufacturing facilities to ensure compliance with current Good Manufacturing Practices (cGMP) before NDA approval[124]. - The Right to Try Act allows certain patients to access investigational drugs post-Phase I trials without enrolling in clinical trials, although manufacturers are not obligated to provide access[116]. - The FDA may issue an approval letter or a complete response letter based on the evaluation of the NDA, with resubmissions reviewed in two to six months[137]. - Post-approval requirements include ongoing regulation by the FDA, which mandates recordkeeping, periodic reporting, and adverse experience reporting[139]. - Drug manufacturers must register with the FDA and are subject to unannounced inspections to ensure compliance with cGMP requirements[140]. - The FDA can withdraw approval if regulatory compliance is not maintained or if new safety issues arise post-market[141]. - The FDA regulates marketing and promotion of drugs, prohibiting claims about safety or effectiveness before approval[142]. Market Access and Pricing - Coverage and reimbursement for pharmaceutical products depend significantly on third-party payors, with uncertainty regarding their decisions impacting sales[192]. - The company may need to conduct expensive pharmacoeconomic studies to secure coverage and reimbursement for its products[193]. - Governments are increasingly implementing cost-containment measures, including price controls, which could limit revenue from approved products[196]. - Pricing negotiations in the EU can be complex, with some countries requiring additional studies to compare cost-effectiveness before granting reimbursement[200]. - Many EU countries have increased the required discounts on pharmaceuticals, intensifying pressure on healthcare costs[201]. Compliance and Legal Regulations - The company is subject to various federal and state healthcare laws and regulations, including the federal Anti-Kickback Statute, which prohibits inducements for referrals or purchases related to federal healthcare programs[204]. - The federal civil and criminal false claims laws, including the civil False Claims Act, prohibit presenting false claims for payment to the federal government[204]. - The Health Insurance Portability and Accountability Act (HIPAA) imposes obligations regarding the privacy and security of individually identifiable health information[204]. - The Foreign Corrupt Practices Act (FCPA) prohibits improper payments to non-U.S. officials to obtain or retain business[204]. - The federal Physician Payments Sunshine Act requires manufacturers to report payments and transfers of value to physicians and teaching hospitals annually[204]. - State laws may require pharmaceutical companies to comply with voluntary compliance guidelines and report payments to healthcare providers[205]. - Compliance efforts are complicated by varying state and foreign laws governing the privacy and security of health information[205].