On June 3, 2020 Seattle Genetics, Inc. (Nasdaq:SGEN) reported that management will participate in a fireside chat during the virtual Goldman Sachs 41st Annual Global Healthcare Conference on Tuesday, June 9, 2020 at 11:20 a.m. Eastern Time (Press release, Seattle Genetics, JUN 3, 2020, View Source [SID1234560799]). The presentation will be webcast live and available for replay from Seattle Genetics’ website at www.seattlegenetics.com in the Investors section.

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On June 3, 2020 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biotechnology company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, reported that its BTK inhibitor BRUKINSA (zanubrutinib) has received approval from the China National Medical Products Administration (NMPA) in two indications – the treatment of adult patients with chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) who have received at least one prior therapy, and the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy (Press release, BeiGene, JUN 3, 2020, View Source [SID1234560798]). Both new drug applications (NDAs) were previously granted priority review by the Center for Drug Evaluation (CDE) of the NMPA.

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BRUKINSA received accelerated approval from the U.S. Food and Drug Administration (FDA) as a treatment for MCL in adult patients who have received at least one prior therapy in November 2019.

"The concurrent approvals of BRUKINSA in R/R CLL/SLL and R/R MCL are a tribute to the collective expertise and hard work of the BeiGene team. With two product approvals covering four indications in China and one in the United States in merely seven months, we continue to focus on execution in advancing our broad portfolio," commented John V. Oyler, Co-Founder, Chief Executive Officer, and Chairman of BeiGene.

"Following in the footsteps of tislelizumab, BRUKINSA is the second BeiGene internally-developed drug approved in China, another significant expansion in our growing commercial portfolio. These approvals would not have been possible without the many clinicians and patients who participated in our trials and the support of the health authorities," commented Xiaobin Wu, Ph.D., General Manager of China and President of BeiGene. "We look forward to launching BRUKINSA in China, a potentially best-in-class BTK inhibitor with extensive global data from nine Phase 3 or potentially registration-enabling studies including a head-to-head comparison trial that was recently presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting."

The NMPA Approval in R/R CLL/SLL

The NMPA approval of BRUKINSA in patients with R/R CLL/SLL is based on results from a single-arm pivotal Phase 2 trial conducted in 91 patients (82 with R/R CLL; nine with R/R SLL) in China (NCT03206918; BGB-3111-205). Clinical efficacy data in the BRUKINSA label in China, as assessed by independent review committee (IRC) per iwCLL 2008 criteria for CLL and Lugano Classification 2014 for SLL, include an overall response rate (ORR) of 62.6%, including a complete response (CR) rate of 3.3%, a partial response (PR) rate of 59.3%, and the PR with lymphocytosis (PR-L) rate was 22%.

The most common adverse reactions reported in the label in China (≥10%) were neutropenia (68.1%), thrombocytopenia (40.7%), hematuria (35.2%), purpura (34.1%), anemia (23.1%), leukopenia (18.7%), pneumonia (18.7%), upper respiratory tract infection (15.4%), hemorrhage (14.3%), and rash (12.1%). The incidence of Grade ≥3 adverse reactions was 69.2%. The incidence of serious adverse reactions was 19.8%, and the most common serious adverse reaction was pneumonia (11.0%).

"The approval of BRUKINSA will provide an important treatment option for Chinese patients with relapsed/refractory CLL/SLL. In addition to BRUKINSA’s significant anti-tumor activity evidenced by an ORR of more than 60%, the drug demonstrated a favorable safety and tolerability profile," commented Jianyong Li, M.D., Professor and Director of the Department of Hematology and Director of the Pukou CLL Center at the First Affiliated Hospital of Nanjing Medical University.

The NMPA Approval in R/R MCL

The NMPA approval of BRUKINSA in patients with R/R MCL is based on results from a single-arm pivotal Phase 2 trial conducted in 86 patients in China (NCT03206970; BGB-3111-206). Clinical efficacy data in the BRUKINSA label in China, as assessed by IRC per Lugano Classification 2014, include the ORR of 83.7%, including a CR rate of 68.6% and a partial response PR rate of 15.1%.

The most common adverse reactions (≥10%) reported in the label in China were neutropenia (47.7%), rash (32.6%), leukopenia (31.4%), thrombocytopenia (30.2%), and anemia (11.6%). The incidence of serious adverse reactions was 15.1%, and common serious adverse reactions (≥2%) included pneumonia (8.1%), hemorrhage (2.3%), and thrombocytopenia (2.3%).

"BRUKINSA has shown promise in hematologic malignancies including in patients with relapsed/refractory MCL. With robust results including a 68.6% CR rate in the MCL trial, we are optimistic and excited about the clinical benefits BRUKINSA can bring to these patients," said Jun Zhu, M.D., Ph.D., Professor and Director of the Department of Internal Medicine and Lymphoma, Peking University Cancer Hospital.

The recommended dose of BRUKINSA in Chinese Package Insert is 160 mg twice daily taken orally with or without food. The dose may be adjusted for adverse reactions, and reduced for patients with severe hepatic impairment and certain drug interactions.

About Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are forms of non-Hodgkin lymphoma, a type of blood cancer, that arise from B lymphocytes. CLL and SLL are essentially the same disease, with the only difference being the location where the cancer primarily occurs.i When most of the cancer cells are located in the peripheral blood and the bone marrow, the disease is referred to as CLL, although the lymph nodes and spleen are often involved. When the cancer cells are located mostly in the lymph nodes, the disease is called SLL.ii According to epidemiological statistics, 88,200 patients are newly diagnosed with lymphoma each year in China, with NHL accounting for approximately 91%. Among all the NHL incidences, patients with B-cell NHL account for 66%, and CLL or SLL accounts for approximately 6.4% of all B-cell NHL incidences, indicating that the number of patients with CLL/SLL reaches approximately 3,390 in all patients (88,200) newly diagnosed with lymphoma each year.iii

About Mantle Cell Lymphoma

Lymphoma is a diverse group of cancers that originate from B-, T- or NK-cells. MCL is typically an aggressive form of non-Hodgkin’s lymphoma (NHL) that arises from B-cells originating in the "mantle zone."iv According to epidemiological statistics, 88,200 patients are newly diagnosed with lymphoma each year in China, with NHL accounting for approximately 91%. Among all the NHL incidences, patients with B-cell NHL account for 66%, and MCL accounts for approximately 5% of B-cell NHL incidences, equivalent to over 2,600 newly diagnosed cases each year.v MCL usually has a poor prognosis, with a median survival of three to four years,vi and is often diagnosed at a later stage of disease.

About BRUKINSA (zanubrutinib)

BRUKINSA (zanubrutinib) is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad pivotal clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies.

BRUKINSA was granted accelerated approval by the U.S. FDA to treat adult patients with MCL who have received at least one prior therapy in November 2019. This accelerated approval is based on overall response rate (ORR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. BRUKINSA was granted approval in China for the treatment of MCL in adult patients who have received at least one prior therapy and CLL or SLL in adult patients who have received at least one prior therapy in May 2020.

BRUKINSA is not approved for use outside of the United States and China.

IMPORTANT U.S. SAFETY INFORMATION FOR BRUKINSA (ZANUBRUTINIB)

Warnings and Precautions

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher bleeding events including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 2% of patients treated with BRUKINSA monotherapy. Bleeding events of any grade, including purpura and petechiae, occurred in 50% of patients treated with BRUKINSA monotherapy.

Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.

Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections

Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 23% of patients treated with BRUKINSA monotherapy. The most common Grade 3 or higher infection was pneumonia. Infections due to hepatitis B virus (HBV) reactivation have occurred.

Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (27%), thrombocytopenia (10%) and anemia (8%) based on laboratory measurements, were reported in patients treated with BRUKINSA monotherapy.

Monitor complete blood counts during treatment and treat using growth factor or transfusions, as needed.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinoma, have occurred in 9% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was skin cancer (basal cell carcinoma and squamous cell carcinoma of skin), reported in 6% of patients. Advise patients to use sun protection.

Cardiac Arrhythmias

Atrial fibrillation and atrial flutter have occurred in 2% of patients treated with BRUKINSA monotherapy. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher events were reported in 0.6% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.

Embryo-Fetal Toxicity

Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for at least 1 week after the last dose. Advise men to avoid fathering a child during treatment and for at least 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

Adverse Reactions

The most common adverse reactions in > 10% of patients who received BRUKINSA were neutrophil count decreased (53%), platelet count decreased (39%), upper respiratory tract infection (38%), white blood cell count decreased (30%), hemoglobin decreased (29%), rash (25%), bruising (23%), diarrhea (20%), cough (20%), musculoskeletal pain (19%), pneumonia (18%), urinary tract infection (13%), hematuria (12%), fatigue (11%), constipation (11%), and hemorrhage (10%). The most frequent serious adverse reactions were pneumonia (11%) and hemorrhage (5%).

Of the 118 patients with MCL treated with BRUKINSA, 8 (7%) patients discontinued treatment due to adverse reactions in the trials. The most frequent adverse reaction leading to treatment discontinuation was pneumonia (3.4%). One (0.8%) patient experienced an adverse reaction leading to dose reduction (hepatitis B).

Drug Interactions

CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For coadministration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.

CYP3A Inducers: Avoid coadministration with moderate or strong CYP3A inducers.

Specific Populations

Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.

INDICATION

BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Please see full U.S. Prescribing Information at beigene.com/PDF/BRUKINSAUSPI.pdf and Patient Information at beigene.com/PDF/BRUKINSAUSPPI.pdf

About the Zanubrutinib Clinical Trial Program

Clinical trials of zanubrutinib include:

Fully-enrolled Phase 3 ASPEN clinical trial in patients with Waldenström’s macroglobulinemia (WM) comparing zanubrutinib to ibrutinib (NCT03053440), currently the only approved BTK inhibitor for WM;
Phase 3 SEQUOIA trial comparing zanubrutinib with bendamustine plus rituximab in patients with treatment-naive (TN) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (NCT03336333);
Phase 3 ALPINE trial comparing zanubrutinib to ibrutinib in patients with relapsed/refractory (R/R) CLL/SLL (NCT03734016);
Phase 2 trial in combination with GAZYVA (obinutuzumab) in patients with R/R follicular lymphoma (FL) (NCT03332017);
Phase 3 trial comparing zanubrutinib and rituximab to bendamustine and rituximab in patients with untreated MCL (NCT04002297);
Phase 2 MAGNOLIA trial in patients with R/R marginal zone lymphoma (MZL) (NCT03846427);
Phase 2 ROSEWOOD trial (NCT03332017) in China comparing obinutuzumab and zanubrutinib vs obinutuzumab alone in treating patients with R/R FL;
Phase 2 trial (NCT04382586) in the U.S. comparing zanubrutinib plus supportive care, to placebo plus supportive care for the treatment of patients with COVID-19 disease and pulmonary distress
Phase 2 trial (NCT03332173) in China in patients with WM; and
Completed Phase 2 trials in China in patients with R/R MCL (NCT03206970) and R/R CLL/SLL (NCT03206918).

On June 3, 2020 Allakos Inc. (Nasdaq: ALLK), a biotechnology company developing antolimab (AK002) for the treatment of eosinophil and mast cell related diseases, reported that it is recruiting patients for two previously announced registrational clinical studies of AK002; a Phase 3 study in eosinophilic gastritis (EG) and/or eosinophilic duodenitis (EoD) and a Phase 2/3 study in eosinophilic esophagitis (EoE) (Press release, Allakos, JUN 3, 2020, View Source [SID1234560797]). Top-line safety and efficacy results from both studies are expected in the second half of 2021. The Phase 3 EG and/or EoD study and the Phase 2/3 EoE study follow positive results from ENIGMA, the Company’s multicenter, randomized, double-blind, placebo-controlled Phase 2 study in patients with EG and/or EoD.

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Phase 3 Eosinophilic Gastritis (EG) and/or Eosinophilic Duodenitis (EoD) Study Design
The multicenter, randomized, double-blind, placebo-controlled Phase 3 study will enroll approximately 160 patients with active, biopsy-confirmed EG (eosinophil count of ≥30 eosinophils in 5 high powered fields [hpfs] in the stomach) and/or EoD (eosinophil count of ≥30 eosinophils in 3 hpfs in duodenum). Patients will be randomized 1:1 to receive: (a) 1.0 mg/kg of antolimab for the first month followed by five doses of 3.0 mg/kg given monthly, or (b) monthly placebo. The co-primary endpoints of the study are: 1) the proportion of patients achieving ≤ 4 eosinophils in 5 hpfs in the stomach and/or ≤15 eosinophils in 3 hpfs in the duodenum and 2) absolute change in Total Symptom Score (TSS-6: abdominal pain, nausea, bloating, early satiety, abdominal cramping, loss of appetite) measured using the daily patient reported symptom questionnaire used in ENIGMA. The TSS-6 comprises the six most frequent and severe symptoms reported in ENIGMA.

Phase 2/3 Eosinophilic Esophagitis (EoE) Study Design
The multicenter, randomized, double-blind, placebo-controlled Phase 2/3 study will enroll approximately 300 patients with active, biopsy-confirmed EoE (eosinophil count of ≥15 eosinophils in a single hpf). Patients will be randomized 1:1:1 to receive: (a) six antolimab doses of 1.0 mg/kg given monthly, (b) 1.0 mg/kg of antolimab for the first month followed by five doses of 3.0 mg/kg given monthly, or (c) monthly placebo. The co-primary endpoints of the study are: (1) the proportion of patients achieving ≤6 eosinophils in a single hpf and (2) absolute change in dysphagia symptoms measured using a daily patient reported symptom questionnaire known as the Dysphagia Symptom Questionnaire (DSQ).

About Eosinophilic Gastritis, Eosinophilic Duodenitis, and Eosinophilic Esophagitis
Eosinophilic gastritis, eosinophilic duodenitis (previously referred to as eosinophilic gastroenteritis), and eosinophilic esophagitis are severe inflammatory orphan diseases characterized by the presence of high levels of eosinophils in the stomach, duodenum, or esophagus, respectively. Common symptoms of the diseases include severe abdominal pain, nausea, diarrhea, bloating, cramping, early satiety, loss of appetite, vomiting, dysphagia, and weight loss. The current estimated prevalence of eosinophilic gastritis and eosinophilic duodenitis in the United States is approximately 50,000 people. The estimated prevalence of eosinophilic esophagitis in the United States is approximately 150,000 people. The Company believes that these diseases may be significantly under-diagnosed, or misdiagnosed, as other gastrointestinal diseases. There are no treatments approved specifically for these diseases. Treatment with systemic steroids can provide symptomatic improvement, but long-term treatment with steroids is generally not possible due to the numerous side effects. Allakos has received orphan drug designation for antolimab in eosinophilic gastritis, eosinophilic gastroenteritis, and eosinophilic esophagitis.

On June 3, 2020 Incyte (Nasdaq:INCY) reported that it will present at the following investor conferences during the month of June (Press release, Incyte, JUN 3, 2020, View Source [SID1234560796]):

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Goldman Sachs 41st Annual Global Healthcare Conference (Virtual) on Tuesday, June 9, 2020 at 8:00 am (EDT);
JMP Securities Hematology & Oncology Forum (Virtual) on Thursday, June 18, 2020 at 4:40 pm (EDT); and
BMO Prescriptions for Success Healthcare Conference (Virtual) on Tuesday, June 23, 2020 at 1:30 pm (EDT)
The presentations will be webcast live and can be accessed at Investor.Incyte.com and will be available for replay for 30 days.

On June 3, 2020 Replimune Group, Inc. (NASDAQ: REPL), a biotechnology company developing a series of oncolytic immuno-gene therapies derived from its Immulytic platform, reported financial results for the fiscal fourth quarter and year ended March 31, 2020 and provided a business update (Press release, Replimune, JUN 3, 2020, View Source [SID1234560795]).

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"I am very pleased with our continued progress developing our pipeline of oncolytic immuno-gene therapies. Today we released additional data with RP1 in our lead indications of cutaneous squamous cell carcinoma (CSCC) and anti-PD1 refractory cutaneous melanoma that we believe point to a high probability of success in our registration-directed clinical trial in CSCC and our potentially registrational cohort of patients currently being enrolled with anti-PD1 refractory melanoma. We also reported plans to initiate clinical development of RP1 in anti-PD1 refractory patients with non-small cell lung cancer (NSCLC)," said Philip Astley-Sparke, CEO of Replimune. "We look forward to presenting further clinical updates from our skin cancer programs later in the year, together with single agent safety and efficacy data and initial data in combination with Opdivo from our ongoing Phase 1 clinical trial with our second product candidate, RP2. We believe we have established clinical proof of principle with RP1 in immune-responsive tumor types and that we now have a solid foundation to further establish our product candidates more universally as the second cornerstone of immune-oncology."

Recent Events and Corporate Highlights

Presented new interim clinical data from the Phase 2 portion of the Phase 1/2 clinical trial of RP1 in combination with Opdivo in non-melanoma and melanoma skin cancers that continue to support clinical programs in both CSCC and anti-PD1 refractory melanoma. A link to the data presented can be found here.

New interim data for patients with CSCC treated with RP1 continued to strengthen since the last update provided at the 2019 Society for the Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). Overall four of seven evaluable patients have ongoing complete responses (CRs) and six of seven have an ongoing CR or partial response (PR) as compared to the data presented at SITC (Free SITC Whitepaper) in November 2019, where one out of five patients had a CR and two out of five had a PR. Importantly, we believe that the number of CRs seen to date in advanced CSCC patients with aggressive disease treated with RP1 in combination with anti-PD1 provides clear differentiation for RP1 versus anti-PD1 therapy alone. Overall, the data continues to demonstrate that RP1 in combination with Opdivo is well tolerated, demonstrates immune activation, continues to drive deep and durable responses in patients with CSCC, and provides what we believe to be strong validation of the Company’s clinical development plan.

Early interim data of RP1 in combination with Opdivo in 16 patients with anti-PD1 refractory cutaneous melanoma demonstrated clear activity, including in patients with extensive visceral disease. Five of 16 patients have so far met the formal criteria of a response, including four of whom had previously failed both anti-PD1 and anti-CTLA4 therapies, providing for a minimum final response rate from this cohort of 31%. With a majority of melanoma patients having primary or acquired resistance to checkpoint blockade, we believe that the initial efficacy seen represents a potential new therapeutic option for these patients.

Additional promising data with RP1 combined with Opdivo in patients with anti-PD1 naïve cutaneous melanoma, mucosal melanoma and uveal melanoma were presented. Uveal and mucosal represent difficult to treat melanoma sub-types and the patients enrolled include responding patients who have already failed both anti-PD1 and anti-CTLA4 therapies.

Announced plans to enroll a new 30 patient cohort in anti-PD1 refractory NSCLC into the Phase 2 portion of the clinical trial of RP1 combined with Opdivo and terminate further enrollment of the 30 patient cohort in metastatic bladder cancer. Anti-PD1 refractory NSCLC represents an area of considerable unmet need. RP1 in combination with Opdivo has demonstrated the ability to shrink lung metastases of other tumor types, including in patients with anti-PD1 refractory disease, where administration of RP1 via imaging guidance has been demonstrated to be both feasible and generally well tolerated in the patients treated so far. Additionally, as a result of a new emerging standard of care in metastatic bladder cancer, the Company has elected to terminate enrollment of this cohort.

Manufacturing. The Company has completed construction of and equipped its 63,000 square feet state of the art commercial capacity manufacturing facility in Framingham MA and successfully completed technology transfer activities. The facility has been designed to allow us to produce enough material to cover full global commercialization of all our current product candidates.

Intellectual Property. The Company has made significant progress in developing its intellectual property portfolio during the year, including through the grant of US patents covering its core technology. These include US patent number 10,612,005, which protects the use of an oncolytic virus expressing an inserted gene encoding a fusogenic glycoprotein (thereby intended to increase the extent and immunogenicity of tumor cell death) together with a gene encoding an immune stimulating protein, and US 10,570,377 which protects the use of the Company’s novel strains of herpes simplex virus (HSV) which were identified through an extensive screen of clinical isolates of HSV to identify strains with the greatest ability to kill human tumor cells.

Announced new appointments to the Board. In April the Company announced the appointment of Dieter Weinand as Chairman of the Board of Directors and the appointment of Paolo Pucci as a new member of the Board of Directors. Mr. Weinand succeeds Philip Astley-Sparke who in January transitioned from part time Executive Chairman to full time Chief Executive Officer. The appointments bring international experience within commercial, operational, and strategic functions in the pharmaceutical industry along with extensive experience in the field of oncology.

Amendment of debt facility. On June 1st the Company closed an expansion of its debt facility with Hercules Growth Capital from $30m to $40m and extension of the interest only period. Combined with various cost containment measures, this should allow the Company to fund operations through 2022.
Program Highlights

Replimune is currently developing three oncolytic immuno-gene therapies derived from its Immulytic platform. RP1 is Replimune’s first clinical product candidate and is based on a proprietary new strain of herpes simplex virus armed with a gene encoding a potent fusogenic protein (GALV-GP-R), intended to enhance tumor killing potency, immunogenic cell death and the activation of systemic anti-tumor immune responses, and with a gene encoding the cytokine GM-CSF. RP2 is a version of RP1 that in addition to expressing GALV-GP-R and GM-CSF also expresses a genetically encoded anti-CTLA-4 antibody-like molecule intended to block the inhibition of the initiation of immune response caused by CTLA-4. RP3 is a further armed oncolytic immuno-gene therapy which additionally expresses two immune co-stimulatory activating ligands – CD40L and 4-1BBL – together with anti-CTLA-4 and GALV-GP-R. CD40L activates CD40, with the goal of achieving broad activation of both innate and adaptive immunity, and 4-1BBL activates 4-1BB (CD137), intended to promote the expansion of cellular and memory immune responses.

RP1 in combination with Libtayo in CSCC: Enrollment in the 240-patient registration-directed Phase 2, randomized, controlled clinical trial is ongoing and is expected to take approximately 18 to 24 months with enrollment intended in the US, Australia, Canada, and European countries including the United Kingdom.

RP1 in combination with Opdivo in melanoma, non-melanoma skin cancers, and MSI-H/dMMR tumors: The melanoma cohort has completed accrual and preliminary results were presented on June 3, together with updated data from the enrolling non-melanoma skin cancer (NMSC) cohort. The NMSC cohort is expected to be fully accrued by the end of 2020, representing a delay partially relating to COVID-19 disruptions. Similarly, it is likely that accumulating sufficient data to inform a decision as to whether to pursue MSI-H/dMMR tumors into registration-directed development will be delayed into 2021.

RP1 in combination with Opdivo in anti-PD-1 refractory melanoma patients: In February 2020, the Company initiated recruitment into a new registration-directed 125-patient cohort in the Phase 2 clinical trial of RP1 in combination with Opdivo.

RP1 as monotherapy in solid organ transplant recipients with CSCC: In May 2020, the Company initiated enrollment into a 30 patient Phase 1/2 clinical trial to assess the safety and efficacy of RP1 in liver and kidney transplant recipients with recurrent CSCC.

RP2 alone and in combination with Opdivo: The ongoing Phase 1 clinical trial evaluating the safety, tolerability, and optimal dose for further development of RP2 alone and in combination with Opdivo remains on track, with initial safety and efficacy data from the single agent RP2 part of the clinical trial together with initial data in combination with Opdivo expected to be presented by the end of 2020.

RP3 alone and in combination with anti-PD-1 therapy: The Phase 1 clinical trial of RP3 alone and in combination with anti-PD-1 therapy remains on track to initiate in 2020.
Financial Highlights

Cash Position: As of March 31, 2020, cash, cash equivalents and short-term investments were $168.6 million, as compared to $134.8 million as of March 31, 2019. This increase was primarily related to $99.7 million in net proceeds from financing activities offset by an increase in cash utilized for capital investments associated with our new manufacturing facility and advancing our expanded clinical development plan.

Based on our current operating plan, we believe that our existing cash and cash equivalents and short-term investments along with our debt commitments will enable us to fund our operating expenses and capital expenditure requirements through 2022.
R&D Expenses: Research and development expenses were $11.2 million for the fourth quarter and $38.8 million for the fiscal year ended March 31, 2020, as compared to $5.4 million for the fourth quarter and $22.2 million for the fiscal year ended March 31, 2019. This increase was primarily due to increased clinical and manufacturing expenses driven by the Company’s lead programs and increased personnel expenses. Research and development expenses included $0.7 million in stock-based compensation expenses for the fourth quarter and $3.7 million in stock-based compensation expenses for the fiscal year ended March 31, 2020.

G&A Expenses: General and administrative expenses were $5.2 million for the fourth quarter and $17.4 million for the fiscal year ended March 31, 2020, as compared to $2.4 million for the fourth quarter and $8.8 million for the year ended March 31, 2019. The increase was primarily driven by personnel related costs, professional fees, and facility expansion. General and administrative expenses included $1.0 million in stock-based compensation expenses for the fourth quarter and $4.1 million in stock-based compensation expenses for the fiscal year ended March 31, 2020.

Net Loss: Net loss was $15.8 million for the fourth quarter and $52.6 million for the fiscal year ended March 31, 2020, as compared to a net loss of $6.7 million for the fourth quarter and $30.8 million for the fiscal year ended March 31, 2019.
About CSCC
CSCC is the second most common form of skin cancer and is estimated to be responsible for at least 7,000 deaths each year in the U.S. It currently accounts for approximately 20% of all skin cancers in the U.S., with the number of newly diagnosed cases expected to rise annually. When CSCC invades deeper layers of the skin or adjacent tissues, it is categorized as locally advanced. Once it spreads to other distant parts of the body, it is considered metastatic. Libtayoâ is the only approved therapy in the United States and Brazil, and conditionally approved therapy in the European Union and Canada, for the treatment of locally advanced or metastatic CSCC.

About Melanoma
Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease and occurs when cancer spreads beyond the surface of the skin to other organs. The incidence of melanoma has been increasing steadily for the last 30 years. In the United States, 91,270 new diagnoses of melanoma and more than 9,320 related deaths are estimated for 2018. Globally, the World Health Organization estimates that by 2035, melanoma incidence will reach 424,102, with 94,308 related deaths. Melanoma is mostly curable when treated in its very early stages; however, survival rates are roughly halved if regional lymph nodes are involved.

About RP1
RP1 is Replimune’s lead Immulytic product candidate and is based on a proprietary new strain of herpes simplex virus engineered to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response.