On March 28, 2023 Evaxion Biotech A/S (NASDAQ: EVAX) ("Evaxion" or the "Company"), a clinical-stage biotechnology company specializing in the discovery and development of AI-powered immunotherapies, reported an increased focus on its strategy around its core AI capabilities allowing fast and de-risked development of its pipeline (Press release, Evaxion Biotech, MAR 28, 2023, View Source [SID1234629440]).

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Recently, Evaxion announced that the Company has used its proprietary AI technology to discover a new treatment opportunity that may broaden cancer immunotherapy. Through new cancer targets, so-called ERVs (endogenous retroviruses), it may become possible to treat cancer patients who have until now been considered unresponsive to immunotherapy.

This opens a wide range of opportunities. Notably, it may increase the likelihood of a positive clinical outcome, paving the way for smaller and faster clinical trials. Evaxion’s next clinical program, EVX-03, will target such personalized ERVs and is scheduled to start clinical development in Q4, 2023, subject to additional funding.

CEO, Per Norlén, comments: "Having been at Evaxion for six months, I continue to be excited by the rich potential of our proprietary AI technology, which I believe is world-leading. A natural next step is to maximize the value of our unique AI capabilities by focusing on target discovery and validation and early out-licensing opportunities. We aim to build a pipeline of multiple assets with superior efficacy and diverse partnering opportunities. This is an area where we experience a lot of interest from big pharma."

The immediate benefits of the new focus are that:

Personalized ERVs are fast-tracked to the clinic with EVX-03, using Evaxion’s novel DNA vaccine technology
Early-stage pipeline can be expanded through multiple partnerships
Cash runway is extended significantly through the new focus, clinical trial optimization, and staff reductions
CEO, Per Norlén, explains:

"By optimizing the strategy around EVX 01, we can deliver the Phase 2b interim data in Q4 2023 as planned while deploying important clinical resources to EVX-03, where we are likely to be first in the world bringing a personalized ERV-immunotherapy to cancer patients. In addition, the focus on our core will extend our cash runway towards the end of the year.

On March 28, 2023 DiaMedica Therapeutics Inc. (Nasdaq: DMAC), a clinical-stage biopharmaceutical company focused on developing novel treatments for neurological disorders and kidney diseases, reported a business update and financial results for the year ended December 31, 2022 (Press release, DiaMedica, MAR 28, 2023, View Source [SID1234629438]). Management will host a conference call Wednesday, March 29, 2023, at 7:00AM Central Daylight Time/8:00AM Eastern Daylight Time to discuss its business update and full year 2022 financial results.

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Clinical Developments

ReMEDy2 Phase 2/3 Trial – Clinical Hold Update

In July 2022, the U.S. Food and Drug Administration (FDA) placed a clinical hold on the Company’s Phase 2/3 ReMEDy2 trial following the Company voluntarily pausing patient enrollment in the trial to investigate three unexpected instances of clinically significant hypotension (low blood pressure) occurring shortly after initiation of intravenous (IV) dose of DM199. The hypotension was transient and blood pressure levels of all three patients recovered back to baseline within minutes of stopping the infusion and the patients suffered no ongoing adverse effects.

In October 2022, the Company announced that the FDA continued the clinical hold and requested that the Company perform an additional in-use in vitro stability study of the IV administration of DM199 to fully identify all potential factors causing or contributing to the three unexpected instances of clinically significant hypotension occurring shortly after initiation of the IV dose of DM199. An in-use study includes testing the combination of the IV bag, IV tubing and any materials used during the infusion that come in contact with DM199 and the mechanical infusion pump in a manner that simulates the actual usage in a hospital. In December 2022, DiaMedica received written comments from the FDA clarifying its expectations for the design of the in-use study. These comments were incorporated into the study protocol and submitted to the FDA. In response, the FDA recently indicated that the protocol appeared to be reasonable. The requested in-use study has been initiated and is being performed at an independent laboratory. The study is being conducted in two parts. Part 1 simulates actual use in the hospital and part 2 tests worst-case scenarios such as varying storage durations, temperature(s) and light. Part 1 is complete. DiaMedica believes data from part 1 confirms its conclusions from prior testing that the IV dose administered in the ReMEDy2 study was higher than planned due to the change in IV bag materials and was the cause of the hypotension, and that a dose revision in ReMEDy2 should avoid the clinically significant hypotension. DiaMedica has submitted these results and conclusions to the FDA for feedback and to confirm that all issues of the clinical hold will have been addressed after submission of data from part 2 of the in-use testing anticipated in April 2023.

The FDA also requested information on a potential trypsin impurity contributing to hypotension and methods assays to be used to measure results in the in-use study. The Company provided responses confirming that trypsin was not a measurable impurity and provided updated validated methods assays to the FDA for review. The Company received FDA feedback that the assays developed for the in-use study appear appropriate and its approaches and assessment to the potential trypsin impurity are also acceptable.

"With the completion of the in-use study at hand, we look forward to continuing to work with the FDA to confirm that we have addressed all issues of the clinical hold and then prepare our complete response requesting a lifting of the clinical hold," commented Rick Pauls, DiaMedica’s Chief Executive Officer. "We believe that we’ve addressed the issues raised by the FDA and are optimistic that the results of the in-use study will fully and finally confirm the cause of the hypotensive events."

DiaMedica also announced that it has proactively initiated a Phase 1C open label, single ascending dose (SAD) study of DM199 administered with the Polyvinylchloride (PVC) IV bags used in the ReMEDy2 trial. The purpose of the study is to confirm, with human data, the DM199 serum concentration level achieved with the IV dose and further evaluate safety and tolerability. In the event that the FDA does not agree that the results of the in-use study support the proposed dose revision, the data from this Phase 1C study can be used to support the rationale for the IV dose selected for the ReMEDy2 trial. The Phase 1C study is being conducted in Australia and is intended to enroll up to 15 healthy, adult participants. Enrollment in the study has commenced and preliminary data is expected to be available in May 2023.

"Patient safety is paramount for DiaMedica and we’re pleased to go above and beyond to achieve that end," stated Kirsten Gruis, DiaMedica’s Chief Medical Officer. "Data developed in our Phase 1C study will ensure that we have the correct IV dose level and give confidence to physician investigators once we are able to resume ReMEDy2."

Balance Sheet and Cash Flow

DiaMedica reported total cash, cash equivalents and investments of $33.5 million, current liabilities of $2.2 million and working capital of $31.7 million as of December 31, 2022, compared to total cash, cash equivalents and investments of $45.1 million, $1.5 million in current liabilities and $43.9 million in working capital as of December 31, 2021. The decreases in cash, cash equivalents and investments and in working capital were due to cash used to fund operating activities during the year ended December 31, 2022.

Net cash used in operating activities was $11.5 million and $12.3 million for the years ended December 31, 2022 and December 31, 2021, respectively. Cash used in operating activities is driven primarily by the Company’s net loss, partially offset by a reduction in non-cash share-based compensation and the effects of the changes in operating assets and liabilities.

Financial Results

Research and development (R&D) expenses decreased to $7.8 million for the year ended December 31, 2022, down $1.0 million from $8.8 million for the year ended December 31, 2021. The decrease was driven primarily by reduced costs incurred during 2022 for the wrap-up of the REDUX Phase 2 CKD trial and decreased non-clinical testing costs which were incurred during 2021 in preparation for initiating the Phase 2/3 ReMEDy2 trial. These decreases were partially offset by increased personnel costs associated with expanding the Company’s R&D operations and increased manufacturing process development activities.

General and administrative (G&A) expenses were $6.2 million for the year ended December 31, 2022, up from $4.9 million for the year ended December 31, 2021. The increase was primarily driven by increased directors’ and officers’ liability insurance, increased personnel and professional services costs to support its expanding clinical programs, and increased legal fees for its lawsuit against Pharmaceutical Research Associates Group B.V. These increases were partially offset by a reduction in non-cash, share-based compensation.

Note for U.S. Shareholders

DiaMedica concluded that it should be considered a passive foreign investment corporation (PFIC) for fiscal 2022. Accordingly, DiaMedica has included the required PFIC Information Statement on its website (www.diamedica.com/investors/financial-reports /tax-information) to allow U.S. investors, if desired after consultation with their tax advisors, to make the qualified electing fund (QEF) election on IRS Form 8621 in order to mitigate the potential adverse tax consequences associated with the Company being a PFIC. Each investor will need to review the PFIC tax consequences and available alternative elections with their tax advisor to determine the best course of action in their particular situation.

Conference Call and Webcast Information

DiaMedica Management will host a conference call and webcast to discuss its business update and full year 2022 financial results on Wednesday, March 29, 2023, at 7:00AM Central Time:

Date:

Wednesday, March 29, 2023

Time:

7:00 AM CDT / 8:00 AM EDT

Web access:

View Source

Dial In:

(877) 550-1858

Conference ID:

1754341

Interested parties may access the conference call by dialing in or listening to the simultaneous webcast. Listeners should log on to the website or dial in 15 minutes prior to the call. The webcast will remain available for play back on the Company’s website, under investor relations – events and presentations, following the earnings call and for 12 months thereafter. A telephonic replay of the conference call will be available until April 5, 2023, by dialing (800) 645-7964 (US Toll Free) and entering the replay passcode: 2125#.

About ReMEDy2 Trial

The ReMEDy2 trial is an adaptive design, randomized, double-blind, placebo-controlled trial studying the use of the Company’s product candidate, DM199, to treat acute ischemic stroke (AIS) patients. The trial is intended to enroll approximately 350 patients at 75 sites in the United States. Patients enrolled in the trial will be treated for three weeks with either DM199 or placebo, beginning within 24 hours of the onset of AIS symptoms, with the final follow-up at 90 days. The trial excludes patients treated with tissue plasminogen activator (tPA) and/or mechanical thrombectomy. The study population is representative of the approximately 80% of AIS patients who do not have treatment options today, primarily due to the limitations on treatment with tPA or mechanical thrombectomy. DiaMedica believes that the proposed trial has the potential to serve as a pivotal registration study of DM199 in this patient population.

About DM199

DM199 is a recombinant (synthetic) form of human tissue kallikrein-1 (KLK1). KLK1 is a serine protease (protein) that plays an important role in the regulation of diverse physiological processes including blood flow, inflammation, fibrosis, oxidative stress and neurogenesis via a molecular mechanism that increases production of nitric oxide and prostaglandin. KLK1 deficiency may play a role in multiple vascular and fibrotic diseases such as stroke, chronic kidney disease, retinopathy, vascular dementia, and resistant hypertension where current treatment options are limited or ineffective. DiaMedica is the first company to have developed and clinically studied a recombinant form of the KLK1 protein. The KLK1 protein, produced from the pancreas of pigs and human urine, has been used to treat patients in Japan, China and South Korea for decades. DM199 is currently being studied in patients with acute ischemic stroke (AIS) and patients with chronic kidney disease. In September 2021, the FDA granted Fast Track Designation to DM199 for the treatment of AIS.

On March 28, 2023 (the "Effective Date"), AbbVie Inc. ("AbbVie") entered into an amended and restated revolving credit agreement (the "Second Amended and Restated Revolving Credit Agreement") among AbbVie, as borrower, the lenders and other parties party thereto and JPMorgan Chase Bank, N.A., as administrative agent (in such capacity, the "Agent"), providing for the amendment and restatement, effective as of the Effective Date, of that certain amended and restated revolving credit agreement, dated as of August 27, 2019, among AbbVie, as borrower, the lenders and other parties party thereto and the Agent (Filing, 8-K, AbbVie, MAR 28, 2023, View Source [SID1234629437]). The Second Amended and Restated Revolving Credit Agreement: (i) increases the unsecured revolving credit facility commitments from $4.0 billion to $5.0 billion and (ii) extends the maturity date of the facility from August 27, 2024 to March 28, 2028. The foregoing summary of the Second Amended and Restated Revolving Credit Agreement does not purport to be complete and is subject to, and qualified in its entirety by, the full text of the Second Amended and Restated Revolving Credit Agreement, which is attached as Exhibit 10.1 to this Current Report on Form 8-K and incorporated herein by reference.

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On March 28, 2023 Corvus Pharmaceuticals, Inc. (Corvus or the Company) (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported a business update and reported financial results for the fourth quarter and year ended December 31, 2022 (Press release, Corvus Pharmaceuticals, MAR 28, 2023, View Source [SID1234629435]).

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"Heading into 2023, we are building momentum for CPI-818, our ITK inhibitor, which we believe is well positioned to provide a platform opportunity across cancer and immune diseases," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "This includes a growing body of clinical and preclinical data supporting ITK inhibition across a range of indications. The most encouraging data is in oncology, where enrollment in our Phase 1/1b trial in T cell lymphoma has accelerated and has enabled us both to increase the number of patients treated at the optimum dose and to identify a predictive biomarker that we believe will enrich for patients most likely to benefit from treatment with CPI-818. Looking forward, we are focused on achieving value driving milestones for CPI-818 including interim T cell lymphoma clinical data at upcoming medical meetings and additional preclinical data with CPI-818 in solid tumors at the upcoming AACR (Free AACR Whitepaper) meeting in April. In addition, we have upside potential from ciforadenant and mupadolimab, the clinical development of which are primarily being advanced and funded by partners."

Business Update and Strategy

Prioritized Program: CPI-818 (selective ITK inhibitor)

CPI-818 for T Cell Lymphoma

CPI-818 Phase 1/1b clinical trial results presented at the 64TH American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in December 2022 provided clinical data and in vivo evidence supporting its ongoing development as a therapy for T cell lymphoma and its potential in autoimmune and allergic diseases. Key data from the presentation include:
As of September 2, 2022, there were 1 complete response (CR), 1 nodal CR and 2 partial responses (PR) in 11 evaluable patients in the 200 mg twice per day cohort (identified optimal dose). An additional PR was seen in a patient receiving the 600 mg twice per day dose. No dose limiting toxicities were observed in 43 patients enrolled across four dosing cohorts, and a maximally tolerated dose was not reached at doses as high as 600 mg twice per day.
The 200 mg dose was shown to induce Th1 skewing and both Th2 and Th17 blockade based on findings in peripheral blood samples from several patients and in vitro data demonstrated that it did so in a dose-dependent manner that supported the selection of the 200 mg twice per day optimum dose. The findings of the human and preclinical studies suggest that CPI-818 enhances anti-tumor immunity representing a potentially novel approach to immunotherapy.
Enrollment in the 200 mg cohort has accelerated and is ongoing. As of February 23, 2023, 20 patients were enrolled, including 13 evaluable for tumor response. There have been 1 CR of 24 months duration, 1 equivocal CR awaiting confirmatory PET scan of 13+ months duration (a previous PR), 1 nodal CR of 21 months duration and 1 PR of 7 months duration. Ten patients continue on therapy, including seven that have not yet been evaluated for tumor response. The swimmer and waterfall tumor plots for these patients are shown below.
New CPI-818 predictive biomarker: Corvus has identified a biomarker associated with response to CPI-818. CPI-818 induces a host anti-tumor cell mediated immune response that requires normal functioning T cells. Data from the 200 mg cohort in the Phase 1/1b clinical trial indicates that a minimum absolute lymphocyte count (ALC) above 900 per cubic milliliter of blood is required for tumor response and disease control. Four of eight patients with ALC above 900 have objective responses (those four patients are described above), all eight have disease control (stable disease, PR, CR) and the median progression free survival (PFS) is 28.1 months. No objective responses were seen in five patients (0 of 5) with ALC below 900 and the PFS is 2.1 months. The ALC biomarker is routinely measured, is consistent with CPI-818’s presumed mechanism of action and is present in about 70% of patients based on the Company’s experience to-date. This biomarker has been incorporated as an eligibility criterion in the ongoing Phase 1/1b clinical trial.

Figure 1: Swimmer Plot for Patients in the 200 mg Dose Cohort of the CPI-818 Phase 1/1b Clinical Trial for T Cell Lymphoma. The plot shows the tumor response and duration (months) for patients with various tumor histologies, which are shown on the chart and defined as follows: PTCL-NOS, peripheral T cell lymphoma not otherwise specified; CTCL-SS, cutaneous T cell lymphoma Sezary; CTCL-MF, cutaneous T cell lymphoma mycosis fungoides; AITL, angioimmunoblastic T cell lymphoma; ALCL, anaplastic T cell lymphoma and NKTCL, natural killer T cell lymphoma. The tumor response evaluation are labeled on the chart and are defined as follows: CR, complete response; equivocal CR; PR, partial response; SD, stable disease; PD, progressive disease. Arrows indicate that treatment with CPI-818 is continuing as of the February 23, 2023 data cut-off.

The plot shows the tumor response and duration (months) for patients with various tumor histologies, which are shown on the chart and defined as follows: PTCL-NOS, peripheral T cell lymphoma not otherwise specified; CTCL-SS, cutaneous T cell lymphoma Sezary; CTCL-MF, cutaneous T cell lymphoma mycosis fungoides; AITL, angioimmunoblastic T cell lymphoma; ALCL, anaplastic T cell lymphoma and NKTCL, natural killer T cell lymphoma. The tumor response evaluation are labeled on the chart and are defined as follows: CR, complete response; equivocal CR; PR, partial response; SD, stable disease; PD, progressive disease. Arrows indicate that treatment with CPI-818 is continuing as of the February 23, 2023 data cut-off.

Corvus recently received a communication from the U.S. Food and Drug Administration (FDA) regarding its clinical development plans for CPI-818. Based on the current enrollment rate of its ongoing Phase 1/1b clinical trial, the Company believes that the number of patients treated in this clinical trial would provide adequate safety and preliminary efficacy data to inform the design of a registration Phase 3 randomized clinical trial. As recommended by the FDA, the Company plans to meet with the FDA to discuss such a clinical trial; it is anticipated that this meeting will take place later this year.
Reprioritization of CPI -818 for Atopic Dermatitis

Based on recent progress and data supporting the ongoing development of CPI-818 for T cell lymphoma and other cancers, Corvus has decided to delay its plans to initiate a Phase 1 clinical trial in atopic dermatitis. This decision allows the Company to conserve cash and intensify its focus on T cell lymphoma, which could include conducting a potentially registrational, randomized Phase 3 trial. While Corvus is pausing development of CPI-818 for the treatment of atopic dermatitis, the Company will continue to investigate the potential role of CPI-818 in immune diseases through its ongoing and planned preclinical research and external collaborations.
CPI-818 for HIV

In February 2023, researchers from The University of California San Francisco-Bay Area Center for AIDS Research (UCSF) presented new data at the 30th Annual Conference on Retroviruses and Opportunistic Infections demonstrating the potential of CPI-818 to reduce the need for chronic human immunodeficiency virus (HIV) therapy. The data further highlights the broad therapeutic opportunity for ITK inhibition with CPI-818. Based on this positive data, the UCSF team plans to continue studying the potential for ITK inhibition to be developed within antiproliferative and "block-and-lock" HIV cure strategies.
Partner Led Programs: Ciforadenant (adenosine 2a receptor inhibitor) and Mupadolimab (anti-CD73)

The Kidney Cancer Research Consortium (KCRC) is enrolling a Phase 1b/2 clinical trial evaluating ciforadenant as a potential first line therapy for metastatic renal cell cancer (RCC) in combination with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). The clinical trial is expected to enroll up to 60 patients and initial data is anticipated before the end of 2023.
Angel Pharmaceuticals, Corvus’ partner in China, is enrolling patients in a Phase 1/1b clinical trial of mupadolimab in patients with non-small cell lung cancer (NSCLC) and head and neck squamous cell cancers. In this clinical trial, patients will receive mupadolimab monotherapy or in combination with pembrolizumab.
Financial Results
As of December 31, 2022, Corvus had cash, cash equivalents and marketable securities totaling $42.3 million. This compared to cash, cash equivalents and marketable securities of $69.5 million as of December 31, 2021. Corvus expects full year 2023 net cash used in operating activities to be between approximately $19 million and $22 million, resulting in a projected cash balance of between $20 million and $23 million as of December 31, 2023. Based on its current plans, Corvus expects its cash to fund operations into 2024.

Research and development expenses for the three months and full year ended December 31, 2022 totaled $4.1 million and $24.5 million, respectively, compared to $4.8 million and $29.1 million for the same periods in 2021. In the fourth quarter of 2022, the decrease of $0.7 million was primarily related to a decrease in personnel costs.

The net loss for the three months ended December 31, 2022 was $9.8 million compared to a net loss of $9.2 million for the same period in 2021. Total stock compensation expense for the three months ended December 31, 2022 was $0.6 million compared to $0.7 million for the same period in 2021 and the non-cash loss from the Company’s equity method investment in Angel Pharmaceuticals was $4.6 million for the three months ended December 31, 2022 compared to $2.6 million for the same period in 2021.

Conference Call Details
Corvus will host a conference call and webcast today, Tuesday, March 28, 2023, at 4:30 p.m. ET (1:30 p.m. PT), during which time management will provide a business update and discuss the fourth quarter and full year 2022 financial results. The conference call can be accessed by dialing 1-844-825-9789 (toll-free domestic) or 1-412-317-5180 (international) or by clicking on this link and requesting a return call and using the conference passcode 3154152. The live webcast may be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus’ website for 90 days.

On March 28, 2023 Blueprint Medicines Corporation (NASDAQ: BPMC) reported that the U.S. Food and Drug Administration (FDA) has lifted a partial clinical hold on the Phase 1/2 VELA trial of BLU-222 (Press release, Blueprint Medicines, MAR 28, 2023, View Source [SID1234629434]).

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On February 10, 2023, Blueprint Medicines announced the FDA placed a partial clinical hold on the VELA trial due to reported visual adverse events, consisting of transient, reversible episodes of light sensitivity and blurred vision, observed in a limited number of patients. Patients already enrolled in the trial have continued receiving study drug. The partial clinical hold is lifted as of March 28, and Blueprint Medicines is working with trial sites to reinitiate patient enrollment.

"With a focus on patient safety, we have worked diligently with the FDA over the last several weeks to resolve the partial clinical hold by updating adverse event monitoring and management procedures. We will now collaborate closely with investigators to resume patient enrollment," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "We are confident in the potential of BLU-222 to improve outcomes in patients with cancers vulnerable to CDK2 inhibition, and we look forward to presenting initial dose escalation data from the VELA trial in the second quarter of 2023.