On August 10, 2021 BioXcel Therapeutics, Inc. ("BioXcel" or the "Company") (Nasdaq: BTAI), a clinical-stage biopharmaceutical company utilizing artificial intelligence approaches to develop transformative medicines in neuroscience and immuno-oncology, reported its financial results for the second quarter ended June 30, 2021 and provided an update on key strategic initiatives (Press release, BioXcel, AUG 10, 2021, View Source [SID1234586188]).

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"During the second quarter, we continued to successfully execute across our clinical, regulatory and commercial objectives for our neuroscience candidate, BXCL501, including furthering our plans for the pivotal Phase 3 program in dementia, executing on our global expansion strategy, and advancing through the regulatory review process," said Vimal Mehta, Ph.D., CEO of BioXcel. "With acceptance of our NDA by the FDA, we are one step closer to our first-ever product approval and making this innovative therapy available to patients suffering from acute agitation associated with schizophrenia and bipolar disorders. We continue to advance our commercial readiness strategy, if approved, and in parallel are advancing our strategic plans for geographic expansion."

Dr. Mehta added, "Looking ahead, we remain confident in the broad potential of BXCL501 across multiple indications where there is significant need for innovative treatments. We remain on track to commence our Phase 3 program for the acute treatment of agitation associated with dementia in the fourth quarter of this year and are exploring additional pipeline opportunities as growth drivers for this business. Looking beyond our neuroscience program, our Phase 1/2b study of BXCL701 for castrate resistant prostate cancer is advancing well, with additional efficacy data from the adenocarcinoma cohort expected in the third quarter 2021. We look forward to building on these successes during the second half of this year."

Company Highlights

Neuroscience Program

BXCL501 is an investigational proprietary, orally dissolving, thin film formulation of the adrenergic receptor agonist dexmedetomidine for the treatment of agitation resulting from neuropsychiatric disorders

Expect to commence the BXCL501 Phase 3 program for the acute treatment of agitation associated with dementia in Q4 2021, pending further feedback from the FDA.

Plan to report topline data from the 40 mcg Phase 2 trial of BXCL501 in patients with acute agitation associated with dementia during Q4 2021.

Received a Prescription Drug User Fee Act ("PDUFA") target action date of January 5, 2022 for the NDA for BXCL501 in the acute treatment of agitation associated with schizophrenia and bipolar disorders I & II.

Plans are underway for a Marketing Authorization Application ("MAA") with the European Medicines Agency ("EMA") of BXCL501 for the acute treatment of agitation associated with schizophrenia and bipolar disorders I & II in 2H 2021.

Initiated pediatric study of BXCL501 for the acute treatment of agitation associated with schizophrenia and bipolar disorders I & II.
Commercial Highlights

Held a Virtual Commercial Day on June 25, 2021, highlighting launch readiness plans in preparation for the potential approval of BXCL501 for the acute treatment of agitation associated with schizophrenia and bipolar disorders I and II.

Continue to advance commercial readiness strategy for the acute treatment of agitation associated with schizophrenia and bipolar disorders I and II.
Medical Affairs Highlights

Presented data from the BXCL501 Phase 3 trials (SERENITY I & II) at the American Psychiatric Association Annual Meeting and at the International Society for Bipolar Disorders 2021 Global Annual Conference and additional data will be presented at a leading medical conference in 2H 2021.

Medical Science Liaison and Medical Manage Care teams continue to engage in scientific and medical-to-medical exchange with healthcare professionals and payers, respectively to provide key insights to support commercial strategy.
Immuno-Oncology Program
BXCL701 is an orally administered systemic innate immune activator for treatment of a rare form of prostate cancer and advanced solid tumors that are refractory or treatment naïve to checkpoint inhibitors.

Data readout from the adenocarcinoma cohort of the Phase 1b/2 trial of BXCL701 and pembrolizumab (KEYTRUDA) in aggressive forms of prostate cancer is planned for Q3 2021.
Corporate Highlights

In June 2021, the Company raised gross proceeds of approximately of $100 million in a common stock offering, providing sufficient cash runway to further fund ongoing clinical development studies and commercialization readiness preparations.
Second Quarter 2021 Financial Results

Research and Development Expenses: Research and development expenses were $13.5 million during the second quarter of 2021, as compared to $17.9 million for the same period in 2020. The decreased expenses were primarily attributable to a reduction in our SERENITY clinical trial costs offset in-part by an increase in personnel and related costs necessary to enlarge our development and medical teams. In addition, we experienced greater professional fees primarily due to increased toxicology studies, regulatory fees and consulting fees, all related to BXCL501.

General and Administrative Expenses: General and administrative expenses were $14.1 million for the second quarter of 2021, as compared to $3.5 million for the same period in 2020. The increase was primarily due to higher stock-based compensation and personnel costs due to our continuing efforts to expand our teams as well as increased marketing and commercial costs related to our preparation of the potential commercial launch of BXCL501 in the U.S., as well as increased legal, professional fees, and insurance costs.

Net Loss: BioXcel reported a net loss of $27.6 million for the second quarter of 2021, compared to a net loss of $21.4 million for the same period in 2020.

The second quarter 2021 results include approximately $6.8 million in non-cash stock-based compensation costs, compared to non-cash stock-based compensation of $2.0 million for the same period in 2020. As of June 30, 2021, cash and cash equivalents totaled approximately $273.1 million.

Conference Call

BioXcel will host a conference call and webcast today at 8:30 a.m. EDT. To access the call, please dial 877-407-2985 (domestic) and 201-378-4915 (international). A live webcast of the call will be available on the Investors section of the BioXcel website, and a replay of the call will be available through at least August 25, 2021. BioXcel’s website is available at www.bioxceltherapeutics.com.

BioXcel may use its website as a distribution channel of material information about the Company. Financial and other important information regarding the Company is routinely posted on and accessible through the Investors sections of its website at www.bioxceltherapeutics.com. In addition, you may automatically receive email alerts and other information about the Company when you enroll your email address by visiting the "Email Alerts" option under the News / Events menu of the Investors section of its website at www.bioxceltherapeutics.com.

On August 10, 2021 Oasmia Pharmaceutical reported that it will publish its Q2 2021 report on August 19, 2021, at 08.00 am CEST (Press release, Oasmia, AUG 10, 2021, View Source [SID1234586180]).

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The company will hold a conference call and an online presentation on the same day at 10.00 am CEST. The call will be hosted by CEO Francois Martelet and CFO Fredrik Järrsten. The presentation will be in English.

The conference call will be broadcast live on the web via the link:
View Source

On August 10, 2021 Clarity Pharmaceuticals, a clinical stage radiopharmaceutical company focused on the treatment of serious disease, reported that the first patient has been dosed in the 64Cu SAR-bisPSMA clinical trial in patients with confirmed prostate cancer (Press release, Clarity Pharmaceuticals, AUG 10, 2021, View Source [SID1234586179]).

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Clarity’s Executive Chairman, Dr Alan Taylor, commented, "We are very excited to have treated our first patient in this clinical trial for men with confirmed prostate cancer using our optimised PSMA agent, 64Cu SAR-bisPSMA, at GenesisCare CTA Medical Clinic in Perth, Australia. We look forward to recruiting additional patients at all three of the clinical sites and generating data to confirm the compelling results from our preclinical studies."

SAR-bisPSMA derives its name from the word "bis", which reflects the novel approach of connecting two PSMA binding motifs to Clarity’s SAR chelator technology (instead of one) to increase tumour uptake and retention in cancerous tissues. Preclinical data confirms that both uptake and retention are higher for 64Cu SAR-bisPSMA than that of the single PSMA binding motif utilised by other radiopharmaceutical products on the market.

The PROPELLER trial is a Phase I Positron Emission Tomography (PET) imaging trial of participants with confirmed prostate cancer using 64Cu SAR-bisPSMA. It is a 30-patient multi-centre, blinded review, dose ranging, non-randomised study of 64Cu-SAR-bisPSMA administered to patients with confirmed prostate cancer prior to radical prostatectomy (NCT04839367)1. The aim of the PROPELLER trial is to determine the safety and tolerability of 64Cu SAR-bisPSMA in participants with untreated, confirmed prostate cancer and planned for radical prostatectomy, as well as compare 64Cu SAR-bisPSMA to 68Ga PSMA-11, the standard of care for prostate cancer imaging in Australia.

Dr Taylor said: "We look forward to further exploring the benefits of the Targeted Copper Theranostics (TCT) platform for patients with prostate cancer, one of the largest indications in oncology. With our 64/67Cu SAR-bisPSMA theranostic trial having commenced last week in the US (SECuRE trial (NCT04868604)2), we believe that Clarity is well positioned to leverage the logistical, manufacturing and treatment benefits associated with the optimised SAR-bisPSMA product and the "perfect pairing" of copper-64 and copper-67 to provide a large patient population with early, accurate and precise detection of prostate cancer and improve patient outcomes. These two trials, PROPELLER and SECuRE, will enable Clarity to get closer to achieving its ultimate goal of improving the treatment of children and adults with cancer."

On August 9, 2021 Aravive Inc. (Nasdaq: ARAV), a clinical-stage oncology company developing innovative therapeutics to treat life-threatening diseases, reported the Company has dosed the first patient in the Phase 1b portion of its Phase 1b/2 trial of AVB-500 in combination with gemcitabine and nab-paclitaxel as a first-line treatment in patients with advanced or metastatic pancreatic adenocarcinoma (Press release, Aravive, AUG 9, 2021, View Source [SID1234594062]). The Phase 1b portion of the clinical trial will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of AVB-500 in combination with gemcitabine and nab-paclitaxel.

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"We are pleased with the quick advancement of AVB-500 with the first patient dosed in our Phase 1b/2 pancreatic adenocarcinoma trial. This clinical trial addresses a very high unmet medical need in one of the most difficult-to-treat cancers with a high mortality rate," said Gail McIntyre, Ph.D., DABT, Chief Executive Officer of Aravive. "We continue to expand the development of AVB-500, as the Company now has three ongoing clinical trials of AVB-500. In addition to the pancreatic adenocarcinoma clinical trial, AVB-500 is currently being investigated in a Phase 3 clinical trial for platinum resistant ovarian cancer and a Phase 1b/2 clinical trial for clear cell renal cell carcinoma."

The Phase 1b/2 clinical trial is designed to evaluate AVB-500 as a first-line therapy in combination with gemcitabine and nab-paclitaxel (Abraxane) in patients with advanced or metastatic pancreatic adenocarcinoma eligible to receive gemcitabine and nab-paclitaxel combination therapy. The Phase 1b portion of the clinical trial will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity in approximately 20 patients dosed with 15 mg/kg of AVB-500 in combination with gemcitabine and nab-paclitaxel. The randomized, controlled Phase 2 portion of the clinical trial is designed to evaluate approximately 60 patients dosed with 15 mg/kg of AVB-500 as a first-line therapy in combination with gemcitabine and nab-paclitaxel versus gemcitabine and nab-paclitaxel alone. The primary endpoint of the Phase 2 portion of the trial is progression-free survival. The secondary endpoints are objective response rate, duration of response, clinical benefit rate, safety and overall survival, and the exploratory endpoints are pharmacokinetics and pharmacodynamics. The Phase 1b/2 trial is listed on clinicaltrials.gov NCT04983407.

About Pancreatic Cancer
Pancreatic cancer is the seventh leading cause of cancer death worldwide. There were approximately 495,800 new cases of pancreatic cancer and 466,000 deaths from the disease worldwide in 2020. It is estimated that there will be approximately 60,400 new cases of pancreatic cancer and 48,200 deaths from the disease in the U.S. in 2021. Pancreatic cancer typically has a poor prognosis, and the five-year survival rate is approximately 11%. Pancreatic adenocarcinoma is the most common type of pancreatic cancer, and there is a clear, high, unmet medical need to improve patient survival with new effective treatments that are safe and well-tolerated. Pancreatic cancer is projected to become the third leading cause of cancer death worldwide by 2025 and the second leading cause of cancer death in the U.S. by 2030.

About AVB-500
AVB-500 is a therapeutic recombinant fusion protein that has been shown to neutralize GAS6 activity by binding to GAS6 with very high affinity in preclinical models. In doing so, AVB-500 selectively inhibits the GAS6-AXL signaling pathway, which is upregulated in multiple cancer types including ovarian, renal and pancreatic cancer. In preclinical studies, GAS6-AXL inhibition has shown anti-tumor activity in combination with a variety of anticancer therapies, including radiation therapy, immuno-oncology agents, and chemotherapeutic drugs that affect DNA replication and repair. Increased expression of AXL and GAS6 in tumors has been correlated with poor prognosis and decreased survival and has been implicated in therapeutic resistance to conventional chemotherapeutics and targeted therapies. AVB-500 is currently being evaluated in multiple clinical trials and has been granted Fast Track Designation by the U.S. Food and Drug Administration in platinum resistant recurrent ovarian cancer. Analysis of all safety data to date showed that AVB-500 has been generally well tolerated with no dose-limiting toxicities or unexpected safety signals.

On August 9, 2021 Race Oncology Limited ("Race") reported that the first patient has been dosed in the Phase 1b/2 trial in relapsed/refractory Acute Myeloid Leukaemia (ASX Announcement: 22 June 2021) (Press release, Race Oncology, AUG 9, 2021, View Source [SID1234591494]).

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This investigator-led trial supervised by Professor Arnon Nagler will use Zantrene (bisantrene dihydrochloride) in a novel three drug combination which has demonstrated compelling efficacy in pre-clinical studies (ASX Announcement: 10 May 2021). Prof Nagler was the Principal Investigator of the Phase 2 investigator-initiated trial where Zantrene was used as a single agent in R/R AML patients and reported an impressive 40% clinical response rate (ASX Announcement: 16 June 2020).

"We are delighted to see the start of this important clinical project which uses a novel combination approach for relapsed or refractory Acute Myeloid Leukaemia. This study is also an important step in our journey towards approval of Zantrene in this area of high unmet medical need."

Race CMO Dr David Fuller
The trial will run in parallel with a separate Australian Phase 2 trial in patients with extramedullary AML (ASX Announcement: 2 June 2021).

Both trials are key components of Race’s Three Pillar strategy.

Even when CR is achieved through intense chemotherapy, approximately half of the younger and 80% of the older patients, relapse. In both clinical situations, refractory and/or relapsed AML, active disease remains a major therapeutic challenge despite recent advances in the clinic.

"This study led by Professor Nagler who has good experience with Zantrene, supports the building of additional data in AML in line with our Three pillar strategy plan. We hope to see improved patient outcomes in what has been historically a difficult to treat disease. We plan on using our trademarked name, Zantrene, in referring to bisantrene dihydrochloride. It’s one of our registered trademarks and its protection is enhanced by its ongoing and appropriate use."

Race CEO & MD Phillip Lynch
Relapsed or Refractory Acute Myeloid Leukemia
Primary refractory or relapsed Acute Myeloid Leukemia is associated with poor prognosis and remains a serious therapeutic challenge. Primary refractory AML is defined by the absence of complete remission (CR), manifested by blast count of ≥5% in bone marrow after one or two cycles of intense induction chemotherapy.

Up to 30% of adults with newly diagnosed AML fail to achieve CR after two courses of intensive chemotherapy.

Clinical Trial Design
The trial is an open-label, Phase 1b/2 study of intravenous FluCloZan (Fludarabine, Clofarabine, Zantrene) in cohorts of up to 12 adult patients with R/R AML with a Phase 1b dose escalation stage to establish the maximum tolerated dose (MTD) or recommended Phase 2 dose of the combined FluCloZan regimen, followed by a Phase 2 expansion stage to determine efficacy and confirm safety of FluCloZan at the recommended Phase 2 dose in up to 17 patients.

Phase 1b, Dose-Escalation (Lead-in Stage)
A two-cohort dose escalation schema using a standard 3 + 3 design will be employed.

Cohort 1 will enroll three patients to receive the FluCloZan regimen for four consecutive days. If no dose limiting toxicities (DLTs) have occurred in the first three patients by day 30 of their first cycle of treatment, then Cohort 2 will receive the treatment for five days (with the extra day representing dose escalation).

Phase 2, Expansion (Efficacy Stage)
Up to 17 patients will be enrolled into a Phase 2 expansion efficacy cohort using a 2-stage Simon design. Initially, 9 patients will be enrolled and treated with the recommended Phase 2 dose of FluCloZan as determined in the Phase 1b part of the study. If there are no patient responses in the first nine subjects according to the response criteria outlined in the European Leukemia Net (ELN) guidelines, the study will be terminated for futility. If at least one patient shows a response, eight more patients will be enrolled and treated. If three or more of the patients treated in Stage 2 respond, the null hypothesis of treatment futility can be rejected.

Efficacy assessments will be based on bone marrow examination at a minimum of two time points on Day 21 and on Day 30. A further bone marrow examination may be performed on Day 42 at the investigator’s discretion, based on patient’s disease and performance status and/or on peripheral blood hematology results during the treatment course and between Day 21 to 42.

Treatment will be terminated upon any sign of progressive/recurrent disease and/or referral to pre-transplant conditioning therapy for (allogeneic) stem cell transplantation.

Patients who do not progress or experience any DLTs may receive a second course of treatment for the same duration as in their first cycle.

All patients will be actively followed-up every three months for a further 12 months following completion treatment for disease free survival (DFS) and overall survival (OS).

Indicative Costs and Timelines
The trial is expected to take 36 to 40 months to complete with full patient recruitment over approximately 18 months. Given the trial is open-label, Race expects that data will be reported at interim points throughout the trial.

Race will pay Chaim Sheba a total fee of USD $668,739 over the study’s life. Payments will be made to Chaim Sheba upon reaching key milestones and the total trial cost will depend on the number of patients recruited and other operational variables.

Clinical Trial Summary
Study Title An Open-label, Phase Ib/II, Two-stage, Study of Zantrene (Bisantrene) in combination with Fludarabine and Clofarabine as Salvage Therapy for Adult Patients with Relapsed or Refractory Acute Myeloid Leukaemia (AML)
Registration NCT04989335
Phase of Development Phase 1b/2
Active Ingredient Bisantrene dihydrochloride, Fludarabine, Clofarabine (FluCloZan)
Study Description Phase 1b/2 study of FluCloZan, IV, in cohorts of adult patients with R/R AML using a 2-stage design: a Phase 1b lead-in dose escalation stage to establish the MTD or RP2D of FluCloZan and a Phase 2 expansion stage to determine efficacy and confirm safety of the FluCloZan regimen at the RP2D.
Principal Investigator Professor Arnon Nagler
Sponsor Race Oncology
Indication/population Adult men and women 18 to 65 years of age with relapsed and/ or refractory Acute Myeloid Leukemia (R/R AML) presenting with non-CNS extramedullary disease.
Number of Subjects Phase 1b: up to 12 patients Phase 2: up to 17 patients in the expansion phase
Study Period 36 – 40 months
Study Design A two-cohort dose escalation schema using a standard 3 + 3 design will be employed followed by an expansion phase at the RP2D. As the patient population is considered relapsed and/or refractory to existing treatments, a comparator arm will not be used.
Statistical methods Simon 2 stage design
End Points Primary
Phase 1b Dose Escalation: number of subjects experiencing a DLT in each cohort Phase 2 Expansion: Overall Response Rate (ORR) defined as the proportion of subjects with CR and CRi between Day 30 to Day 42 Secondary: Transplant/allo-HSCT rates (for transplant/allo-HSCT-eligible subjects); Combined CR and CRi and PR response rate; Morphologic leukemia-free state (MLFS); Partial remission (PR); Stable disease (SD); Progressive disease (PD); Relapse; Disease free survival (DFS); Overall survival (OS); Time to next treatment (for transplant/allo-HSCT-ineligible subjects)
Participating Centres 1 Chaim Sheba Medical Center, Tel Hashomer, Israel
Dates First patient August 6, 2021; Last patient (anticipated): Q3 CY2023