Docetaxel/Ritonavir

ModraDoc006/r at 20-20/200-100mg dosage eliminated neutropenia and significantly decreased neuropathy while maintaining efficacy levels comparable to intravenous (IV) docetaxel Based on strong safety data and encouraging efficacy from the randomized Phase 2b trial, the 20-20/200-100mg dose has been selected for use in planned Phase 3 clinical trial AMSTERDAM--(BUSINESS WIRE)-- Modra Pharmaceuticals (“Modra”) today announced the final results of the lower dose cohort in the Company’s Phase 2b trial evaluating its oral taxane therapeutic, ModraDoc006/r, in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC) compared to standard-of-care IV chemotherapy docetaxel at 75 mg/m2 Q3W. ModraDoc006/r is an oral tablet formulation of docetaxel co-administered with ritonavir, a boosting agent which enhances bioavailability. The lower 20-20/200-100mg dose demonstrated a significantly improved safety pro to IV docetaxel while maintaining efficacy levels. Based on these encouraging results, this optimal dose has been selected for Modra’s planned Phase 3 pivotal trial in mCRPC patients. The Phase 2b data will be presented in a “poster discussion” presentation at the ASCO Annual Meeting 2022, held from June 3 – 7. “The detailed analysis of the lower dose cohort has demonstrated that we can further improve the safety pro ModraDoc006/r without compromising activity, making it a very attractive option to deliver chemotherapy. Now, with the optimal dosage of ModraDoc006/r selected, we are well-positioned to enter Phase 3 clinical testing and get one step closer to bringing a safer, effective and more convenient alternative to IV chemotherapy to patients living with mCRPC,” said Colin Freund, CEO of Modra Pharmaceuticals. Out of the 62 patients enrolled in the second cohort, 31 received IV docetaxel and 31 were administered ModraDoc006/r at 20mg ModraDoc006 combined with 200mg ritonavir in the morning, 20mg ModraDoc006 with 100mg ritonavir in the afternoon (“20-20/200-100”) in a bi-daily weekly dosing (BIDW) regimen. Notably, neutropenia was eliminated with ModraDoc006/r 20-20; 0% vs. 26% on IV docetaxel. Neuropathy was significantly reduced at 10% G1 only on ModraDoc006/r vs. 29% total (10% G1, 19% G2) on IV docetaxel. Incidence of alopecia was 23% on ModraDoc006/r vs. 42% on IV docetaxel. ModraDoc006/r vs. IV docetaxel demonstrated an overall response rate (ORR) of 39% vs. 29% respectively. Prostate-Specific Antigen (PSA) responses were also comparable at 48% vs. 50%. Gastrointestinal toxicities with ModraDoc006/r 20-20 remained mild and similar to IV docetaxel. “Not only did ModraDoc006/r 20-20 eliminate neutropenia, a significant hurdle in the oral taxane space, while maintaining equivalent efficacy to IV docetaxel, it also dramatically reduced neuropathy and alopecia, side-effects that frequently complicate the lives of mCRPC patients undergoing chemotherapy,” said Ulka Vaishampayan, MD, Principal Investigator of the study and Professor of Internal Medicine, Division of Hematology/Oncology at the University of Michigan. “These encouraging data provide a compelling rationale for conducting further development in a pivotal study with ModraDoc006/r to further investigate its potential. ModraDoc006/r 20-20 will be applicable to a broader mCRPC patient population that may not have access to or tolerate more traditional IV chemotherapy regimens. The convenience of oral administration with maintained efficacy makes it an attractive option that is likely to improve prostate cancer outcomes.” The open label 1:1 randomized study compared ModraDoc006/r 20-20 in a BIDW schedule with IV docetaxel 75 mg/m2 administered in 21-day cycles. Participating patients had mCRPC with a performance status of 0-1 and had not received prior chemotherapy for mCRPC. All patients received 5 mg oral prednisone twice daily. The primary endpoint of the study was radiographic progression free survival (rPFS) per PCWG-3 criteria. Secondary objectives included ORR, PSA-PFS, time to skeletal related events, disease control rate, duration of response and safety assessments. Presentation Details Session: Genitourinary Cancer—Prostate, Testicular, and Penile Poster Title: A Phase 2 randomized study of oral docetaxel plus ritonavir (ModraDoc006/r) in patients with metastatic castration-resistant prostate cancer (mCRPC) Presenter: Ulka N. Vaishampayan, MD | University of Michigan Location: In-Person & Live Stream | Arie Crown Theater Session Date and Time: June 6, 2022 from 16:30 CDT – 18:00 CDT Abstract Number: 5016 Poster Number: 200 About metastatic Castration-Resistant Prostate Cancer (mCRPC) mCRPC is an advanced form of prostate cancer and the fourth most common cause of cancer death overall. mCRPC is not amenable to surgical treatment and resistant to androgen deprivation therapy, a hormone therapy used as initial disease management to reduce growth of prostate cancer cells. About ModraDoc006/r ModraDoc006/r is a proprietary boosted taxane therapy based on docetaxel, an intravenously administered therapy, that is very broadly used in a variety of tumor types. ModraDoc006 – an oral docetaxel tablet - is given in combination with ritonavir (r), which acts as a booster to increase the systemic bioavailability of ModraDoc006. ModraDoc006/r is designed to combine the convenience and practicality of taking chemotherapy treatment at home with the potential for an improved safety profile, as compared to standard IV docetaxel. About Modra Pharmaceuticals Modra Pharmaceuticals aims to transform taxane therapy by developing therapies that are less toxic, at least as effective and can be taken at home in tablet form. The Company’s goal is to dramatically improve the therapeutic outcomes and everyday lives of the hundreds of thousands of cancer patients undergoing taxane therapy worldwide. Modra’s lead program completed a Phase 2b clinical study in prostate cancer, resulting in positive date further supporting the delivery, bioavailability and tolerability of its novel approach. View source version on businesswire.com: Contacts Colin Freund CEO, Modra Pharmaceuticals colin.freund@modrapharmaceuticals.com Tel: +1 609 933 8008 Trophic Communications Valeria Fisher or Desmond James modra@trophic.eu Tel: +49 (0) 175 804 1816 or +49 (0) 1516 7859086 Source: Modra Pharmaceuticals View this news release online at:

Modra Pharmaceuticals (“Modra”) today announced positive data from its Phase IIb trial evaluating its boosted oral taxane therapeutic, ModraDoc006/r, in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC) compared to the standard-of-care, the IV chemotherapy docetaxel. ModraDoc006/r is an oral tablet formulation of docetaxel co-administered with ritonavir, a boosting agent which enhances bioavailability. In a total of 101 patients enrolled, ModraDoc006/r demonstrated a similar efficacy and an improved tolerability pro to IV docetaxel, with reduced neutropenia, neuropathy and alopecia. The trial data will be presented at the 2022 Annual American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) held from February 17-19, 2022, one year after Modra shared its initial study data at the same conference. “Completing this study is an exciting step for Modra, as we continue to demonstrate the potential of ModraDoc006/r to be a valuable alternative to IV chemotherapeutics for mCRPC,” said Colin Freund, CEO of Modra Pharmaceuticals. “Our goal with ModraDoc006/r is to offer a better tolerated, effective and more convenient oral taxane therapeutic to patients with prostate cancer, including those who cannot tolerate or otherwise access IV therapy. Based on the currently reported compelling data, we are planning out the next development steps for ModraDoc006/r, including a pivotal study. We would like to extend our sincere thanks to the patients and clinicians who participated in this study.” Out of the total study population, 49 patients received IV docetaxel and 52 ModraDoc006/r (21 on 30-20/200-100 mg (“30-20”) and 31 on 20-20/200-100 mg (“20-20”) bi-daily weekly dosing (BIDW) doses). ModraDoc006/r vs IV docetaxel demonstrated an overall response rate (ORR) of 44% vs. 39%, respectively. Prostate-Specific Antigen (PSA) responses were comparable at 50% vs. 57%, respectively. Neutropenia (low levels of neutrophils, a type of white blood cell) was eliminated with ModraDoc006/r at the 20-20 mg dose, reduced to 14% at the 30-20 mg dose vs 25% on IV docetaxel. Neuropathy (nerve damage or dysfunction) and alopecia were also reduced with ModraDoc006/r at the 20-20 mg dose compared to the 30-20 mg dose and IV docetaxel. Gastrointestinal toxicities were slightly more frequent, but still predominantly mild, in the ModraDoc006/r arm at both dose levels. “ModraDoc006/r has shown a favorable toxicity pro comparable efficacy to IV docetaxel in metastatic CRPC. Advanced prostate cancer patients frequently do not receive the benefits of IV docetaxel chemotherapy due to advanced age, comorbidities and, during the pandemic, fear of exposure to Covid-19 at infusion centers. An oral chemo that is easier to tolerate - with less risk of cytopenias, hair loss and neuropathy - would make the benefits of chemo accessible to the majority of patients with metastatic prostate cancer. Thus, there is a compelling rationale to evaluate ModraDoc006/r further,” said Ulka Vaishampayan, MD, Principal Investigator of the study and Professor of Internal Medicine, Division of Hematology/Oncology at the University of Michigan. The open label 1:1 randomized study evaluated a ModraDoc006/r BIDW regimen versus IV docetaxel 75 mg/m2 in 21-day cycles. Initially a BIDW 30-20/200-100 mg dose (representing 30 mg ModraDoc006 and 200 mg ritonavir in the morning, 20 mg ModraDoc006 and 100 mg ritonavir in the evening) was administered on days 1, 8 and 15 of a 21-day cycle. After 21 patients, the morning dose of ModraDoc006 was reduced to 20 mg to improve tolerability. All patients received 5 mg oral prednisone twice daily. The primary endpoint of the study was radiographic progression free survival (rPFS) per PCWG-3 criteria. Secondary objectives were ORR, PSA-PFS, time to skeletal related events, disease control rate, duration of response, and safety assessments. Patient reported outcomes and health-related Quality of Life (QoL) was assessed with treatment satisfaction and Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaires at baseline and after cycles 3, 6 and 10. About metastatic Castration-Resistant Prostate Cancer (mCRPC) mCRPC is an advanced form of prostate cancer and the fourth most common cause of cancer death overall. mCRPC is not amenable to surgical treatment and resistant to androgen deprivation therapy, a hormone therapy used as initial disease management to reduce growth of prostate cancer cells. About ModraDoc006/r ModraDoc006/r is a proprietary boosted taxane therapy based on docetaxel, an intravenously administered therapy, that is very broadly used in a variety of tumor types. ModraDoc006 – an oral docetaxel tablet - is given in combination with ritonavir (r), which acts as a booster to increase the systemic bioavailability of ModraDoc006. ModraDoc006/r is designed to combine the convenience and practicality of taking chemotherapy treatment at home with the potential for an improved safety profile, as compared to standard IV docetaxel. About Modra Pharmaceuticals Modra Pharmaceuticals aims to transform taxane therapy by developing therapies that are less toxic, more effective and can be taken at home in tablet form. The Company’s goal is to dramatically improve the therapeutic outcomes and everyday lives of the hundreds of thousands of cancer patients undergoing taxane therapy worldwide. Modra’s lead program completed a Phase 2b clinical study in prostate cancer, resulting in positive date further supporting the delivery, bioavailability and tolerability of its novel approach.