On March 7, 2022 Evaxion Biotech A/S (NASDAQ: EVAX), a clinical-stage biotechnology company specializing in the development of AI-driven immunotherapies, reported that now finalized recruitment for Phase 1/2a clinical trial of EVX-02 in adjuvant melanoma patients (Press release, Evaxion Biotech, MAR 7, 2022, View Source [SID1234609592]).

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The Company already conducts the successful EVX-01 program with clinical testing in Australia, Europe and the US, where app. 100 patients suffering from malignant melanoma (metastasized skin cancer) will be treated with EVX-01 therapy in combination with Keytrudaâ from Merck. In the EVX-02 program, Evaxion treats patients with adjuvant melanoma, meaning that their tumors have been successfully removed (surgically), and in the study the focus of the therapy is to avoid relapse.

In the EVX-02 study encouraging preliminary findings around its potential clinical benefit now allows Evaxion to accelerate the development program. Following the finalization of recruitment, Evaxion will advance into a dedicated Phase 2b clinical trial using its patented DNA-based immunotherapy.

For the patients enrolled in the Phase 1/2a clinical trial, Evaxion’s proprietary PIONEERTM AI technology identified a sufficient number of mutations to design a personalized treatment and so far, no serious side effects have been reported.

Lars Wegner, CEO of Evaxion, said:

"Completion of recruitment for the Phase 1/2a clinical trial of EVX-02 is an important milestone, which supports our belief that the Evaxion approach is feasible. EVX-02 appears to be well tolerated and shows encouraging signs as a treatment for adjuvant melanoma patients. The T-cell activation is promising, which allows us to take data and insights from this clinical trial and move into a dedicated Phase 2 clinical trial."

About the EVX-02 Program:

1.Evaxion Biotech has completed recruitment of 16 patients and will now move directly into a dedicated phase 2b clinical trial in adjuvant melanoma.

2.Final data from the current phase 1/2a clinical trial are expected to be announced and reported second quarter of 2023, which is earlier than previously communicated.

3.Expected milestones for the EVX-02 phase 2b study are: Regulatory filing in H1 2022, First patient first visit in H2 2022 and an interim readout in 2023.

On March 7, 2022 DURECT Corporation (Nasdaq: DRRX) reported financial results for the three months and year ended December 31, 2021 and provided a corporate update (Press release, DURECT, MAR 7, 2022, View Source [SID1234609591]).

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"We are pleased with the progress made over the past few months in the larsucosterol (DUR-928) AHFIRM trial, including opening international sites and the enrollment rate of patients with severe alcohol-associated hepatitis (AH)," stated James E. Brown, D.V.M., President and CEO of DURECT. "We also signed a U.S. licensing agreement for POSIMIR with Innocoll Pharmaceuticals and look forward to their anticipated launch in the second quarter of 2022."

Fourth Quarter and Recent Business Highlights:

Continued progress in AHFIRM enrollment – DURECT has now dosed over 100 patients in the Phase 2b AHFIRM clinical trial of larsucosterol in severe AH. This includes dosing the first patient in Europe, with 51 global AHFIRM study sites now open, an increase of 15 since our last earnings call. With this progress, our estimated completion of enrollment remains on track for mid-2023.
Successful completion of POSIMIR licensing – DURECT signed an exclusive U.S. licensing agreement for POSIMIR with Innocoll Pharmaceuticals in late 2021. Under the agreement, DURECT will earn low to mid double-digit royalties from net sales of POSIMIR and is eligible to receive up to $136 million in upfronts and milestones, including the $4 million upfront license fee received in January 2022, and a $2 million milestone payment upon the first commercial sale of POSIMIR, which is anticipated in 2Q22.
Increasing awareness of AH market potential – In collaboration with DURECT, Dr. Suthat Liangpunsakul presented a poster at The Liver Meeting 2021 showing increased hospitalizations for AH in the U.S., highlighting both significant comorbidities and high hospitalization costs of over $150,000 per hospitalization for those AH patients who died during their hospital stay.
Important addition to our team – In December 2021, DURECT strengthened its board of directors with the appointment of Pete Garcia, a seasoned financial executive in the biopharmaceutical industry.
Financial highlights for Q4 and full year 2021:

Total revenues were $7.3 million and net loss from continuing operations was $7.0 million for the three months ended December 31, 2021 compared to total revenues of $2.2 million and net loss from continuing operations of $8.8 million for the three months ended December 31, 2020. Total revenues were $14.0 million and net loss from continuing operations was $36.3 million for the year ended December 31, 2021, compared to total revenues of $30.1 million and net loss from continuing operations of $14.3 million for the year ended December 31, 2020.
At December 31, 2021, cash and investments were $70.0 million, compared to cash, cash held in escrow and investments of $56.9 million at December 31, 2020. Debt at December 31, 2021 was $20.6 million, compared to $20.8 million at December 31, 2020. At December 31, 2021, accounts receivable included $5.3 million due from Innocoll as a result of the $4 million upfront fee and a $1.3 million fee primarily to cover manufacturing supplies and excipients and certain equipment transferred to Innocoll; these funds were received in January 2022.
Upcoming Key Milestones:

Complete opening of 60 or more global clinical trial sites across the U.S., E.U., U.K., and Australia and continue acceleration of enrollment in the Phase 2b AHFIRM trial of larsucosterol in severe AH
Provide an update on plans to expand clinical development of larsucosterol in NASH and/or other indications
Commercial launch of POSIMIR by our licensee, Innocoll Pharmaceuticals; expected in Q2 2022
Earnings Conference Call

We will host a conference call today at 4:30 p.m. Eastern Time/1:30 p.m. Pacific Time to discuss fourth quarter 2021 results and provide a corporate update:

Monday, March 7 @ 4:30pm Eastern Time / 1:30 p.m. Pacific Time

Toll Free:

877-869-3847

International:

201-689-8261

Conference ID:

13727525

Webcast:

View Source

A live audio webcast of the presentation will be also available by accessing DURECT’s homepage at www.durect.com and clicking "Investors." If you are unable to participate during the live webcast, the call will be archived on DURECT’s website under "Event Calendar" in the "Investors" section.

About the AHFIRM Trial

Enrollment is ongoing in our Phase 2b randomized, double-blind, placebo-controlled, international, multi-center study in subjects with severe acute alcohol-associated hepatitis (AH) to evaluate saFety and effIcacy of laRsucosterol (DUR-928) treatMent (AHFIRM). The study is comprised of three arms targeting enrollment of 300 total patients, with approximately 100 patients in each arm: (1) Placebo plus standard of care (SOC) which may include the use of methylprednisolone, a corticosteroid, at the discretion of the treating physician; (2) larsucosterol (30 mg); and (3) larsucosterol (90 mg). All patients in the trial receive supportive care. The primary outcome measure is 90-day survival rate for patients treated with larsucosterol compared to those treated with placebo plus SOC. The Company is targeting more than 60 clinical trial sites across the U.S., EU, U.K., and Australia. Reflecting the life-threatening nature of AH and the lack of therapeutic options, the U.S. Food and Drug Administration (FDA) has granted larsucosterol Fast Track Designation for the treatment of AH. We believe demonstration of a robust survival benefit in the AHFIRM trial would support an NDA filing. For more information, refer to ClinicalTrials.gov Identifier: NCT04563026.

About Alcohol-associated Hepatitis (AH)

AH is a life-threatening acute alcohol-associated liver disease (ALD) often caused by chronic heavy alcohol use and a recent period of increased alcohol consumption (i.e., a binge). It is characterized by severe inflammation and destruction of liver tissue (i.e., necrosis), potentially leading to life-threatening complications including liver failure, acute renal injury and multi-organ failure. There are no FDA approved therapies for AH and an analysis of 77 studies published between 1971 and 2016, which included data from a total of 8,184 patients, showed the overall mortality from AH was 26% at 28 days, 29% at 90 days and 44% at 180 days. A subsequent global study published in December 2021, which included 85 tertiary centers in 11 countries across 3 continents, prospectively enrolled 2,581 AH patients with a median MELD score of 23.5, reported mortality at 28 and 90 days of 20% and 31% respectively. Stopping alcohol consumption is not sufficient for recovery in many moderate and severe patients and the use of treatments to reduce liver inflammation, such as corticosteroids, are limited by contraindications and have been shown to provide no survival benefit at 90 days or 1 year. While liver transplantation is becoming more common for alcoholic liver disease patients, including for AH patients, the procedure involves a long waiting period, a burdensome selection process, and costs more than $875,000 on average.

About Larsucosterol (DUR-928)

Larsucosterol is an endogenous sulfated oxysterol and an epigenetic regulator. Epigenetic regulators are compounds that regulate patterns of gene expression without modifying the DNA sequence. DNA hypermethylation, an example of epigenetic dysregulation, results in transcriptomic reprogramming and cellular dysfunction, and has been found to be associated with many acute (e.g., AH) or chronic diseases (e.g., NASH). As an inhibitor of DNA methyltransferases (DNMT1, DNMT3a and 3b), larsucosterol inhibits DNA methylation, which subsequently regulates expression of genes that are involved in cell signaling pathways associated with stress responses, cell death and survival, and lipid biosynthesis. This may ultimately lead to improved cell survival, reduced inflammation, and decreased lipotoxicity. As an epigenetic regulator, the proposed mechanism of action provides further scientific rationale for developing larsucosterol for the treatment of acute organ injury and certain chronic diseases.

On March 7, 2022 Biodesix, Inc. (Nasdaq: BDSX), a leading data-driven diagnostic solutions company with a focus in lung disease, reported it has entered into a purchase agreement for the issuance and sale of its common stock, from time to time, of up to $50 million with Lincoln Park Capital Fund, LLC (LPC), a Chicago-based institutional investor (Press release, Biodesix, MAR 7, 2022, View Source [SID1234609590]).

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Under the terms of the purchase agreement, Biodesix will have the right at its sole discretion, but not the obligation, to sell to LPC up to $50 million worth of common stock over the 36-month term of the agreement, subject to certain conditions. There are no upper limits to the price per common stock LPC may pay to purchase the common stock, and the purchase price of the common stock will be based on the prevailing market prices at the time of each sale to LPC. Biodesix controls the timing and amount of any future sales of its common stock to LPC.

There are no warrants, derivatives, financial or business covenants associated with the agreement, and LPC has agreed not to cause or engage in any direct or indirect short selling or hedging of Biodesix’s common stock. Biodesix may terminate the purchase agreement at any time, at its discretion, without any cost or penalty. In consideration for LPC entering into the purchase agreement, Biodesix issued shares of its common stock to LPC as a fee for LPC’s obligation to purchase common stock at the Company’s discretion.

Biodesix intends to use any net proceeds from the sale of its common stock to LPC to advance its growth strategy and for general corporate purposes.

Additional information regarding the purchase agreement with LPC is available in the Current Report on Form 8-K that Biodesix will file with the Securities and Exchange Commission.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy any shares of common stock, nor shall there be any sale of shares of common stock in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or other jurisdiction.

On March 7, 2022 Tollys, a biopharmaceutical company developing TL-532, the first anti-cancer immunotherapy based on a synthetic toll-like receptor 3 (TLR3) specific agonist, reported that it has entered into a sponsored research agreement with Gustave Roussy, the leading cancer center in Europe (Press release, Tollys, MAR 7, 2022, View Source [SID1234609589]).

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Professor Guido Kroemer’s team will evaluate the effects of TL-532 in the context of FPR1 deficiency using methods similar to those recently published in the original research article entitled ‘A TLR3 Ligand reestablishes chemotherapeutic responses in the context of FPR1 deficiency’. These studies were conducted with polyinosinic:polycytidylic acid (pIC), a research grade TLR3 agonist. In comparison with agonists of TLR 2, 4, 5, 6, 7, 8 and 9, only the TLR3 agonist pIC was able to restore deficient chemotherapeutic responses in mice lacking FPR1, suggesting a personalized strategy for compensating for the FPR1 defect with a TLR3 agonist.

TL-532 is developed by Tollys and is a specific TLR3 agonist with a defined 70 base pair sequence of double-stranded RNA (dsRNA), produced by chemical synthesis, which can meet today’s quality manufacturing standards for new molecular entities.

"We are very eager to show that TL-532 can restore deficient chemotherapeutic responses in the model of Prof Kroemer’s team, because FPR1 deficiency is a common genetic disorder and there is a good chance that, in the future, patients with FPR1 deficiency may derive critical benefits from a treatment with TL-532," said Vincent Charlon, CEO of Tollys.

About FPR1 Deficiency
For anthracycline-based chemotherapy to be immunogenic, dying cancer cells must release annexin A1 (ANXA1) that subsequently interacts with the pattern recognition receptor, formyl peptide receptor 1 (FPR1), on the surface of dendritic cells (DC). Approximately 30% of individuals bear loss-of-function alleles of FPR1, calling for strategies to ameliorate their anticancer immune response. Le Naour et al. (Cancer Discovery 2021;11:408-23), showed that immunotherapy with a ligand of Toll-like receptor-3, polyinosinic:polycytidylic acid (pIC), restores the deficient response to chemotherapy in tumors lacking ANXA1 developing in immunocompetent mice or those of normal cancers growing in FPR1-deficient mice. This effect was accompanied by improved DC-and T-lymphocyte–mediated anticancer immunity. Of note, carcinogen-induced breast cancers precociously developed in FPR1-deficient mice as compared with wild-type controls. A similar tendency for earlier cancer development was found in patients carrying the loss-of-function allele of FPR1. These findings have potential implications for the clinical management of FPR1-deficient patients.

About TL-532
TL-532 is the first synthetic specific TLR3 agonist with a proprietary defined doublestranded RNA sequence. As such, TL-532 has the potential to be the best-in-class and firstto-market TLR3 agonist. TL-532 was shown to have a triple mechanism of action inducing 1) death by apoptosis selective to cancer cells-not in normal cells-, leading to the in-situ release of tumor specific antigens, 2) activation of the myeloid dendritic cells of the immune system to mount a specific T-cell response against the tumor antigens and 3) a switch of the tumor microenvironment by producing cytokines and chemokines which are unfavorable to tumor development. The result is the immunogenic cell death of tumor cells, accompanied by an auto-vaccination preventing the recurrence of cancer.

On March 7, 2022 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) and Nippon Shinyaku Co., Ltd. (TOKYO: 4516) reported that Chugai filed a regulatory application with the Ministry of Health, Labour and Welfare (MHLW), for approval of an anti-cancer agent/humanized anti-CD20 monoclonal antibody Gazyva Intravenous Infusion 1000 mg [generic name; obinutuzumab (genetical recombination)] for the treatment of chronic lymphocytic leukemia (CLL) (Press release, Chugai, MAR 7, 2022, View Source [SID1234609587]).

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"Ensuring safety during long-term treatment is increasingly important as the recent expansion in treatment options may lead to longer survival for patients with CLL. As a result, there is a growing unmet medical need for treatments that control disease and have an acceptable safety profile," said Chugai’s President and CEO, Dr. Osamu Okuda. "We are working towards approval of Gazyva so the drug can contribute to treatment as a new therapeutic option for CLL."

"We are very pleased that Gazyva was applied for marketing approval for a new indication in CLL," said Nippon Shinyaku’s President, Toru Nakai. "We believe that the addition of the CLL indication to Gazyva will help medical needs and further contribute to the treatment of patients in the field of hematologic malignancies, which is one of our focus field."

The filing is based on the results including Phase III ELEVATE-TN study (ACE-CL-007) conducted by AstraZeneca, evaluating the efficacy and safety of Gazyva and acalabrutinib (Bruton’s tyrosine kinase (BTK) inhibitor, brand name Calquence) in patients with untreated CLL.

About ELEVATE-TN study
ELEVATE-TN (ACE-CL-007, NCT02475681) study is a randomized, multicenter, open-label Phase III trial evaluating the safety and efficacy of acalabrutinib in combination with obinutuzumab or alone versus chlorambucil (unapproved) in combination with obinutuzumab in previously untreated patients with CLL. In the study, patients are randomized 1:1:1 to following groups;

Chlorambucil plus obinutuzumab
Acalabrutinib plus obinutuzumab
Acalabrutinib monotherapy
The primary endpoint is IRC-assessed progression-free survival (PFS) with acalabrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab. Secondary endpoint is IRC-assessed PFS with acalabrutinib monotherapy versus chlorambucil plus obinutuzumab. Other secondary endpoints are objective response rate, time to next treatment and overall survival etc 1).

About Gazyva (obinutuzumab)
Gazyva is a glycoengineered type II anti-CD20 monoclonal antibody designed to bind to CD20, a protein expressed on certain B cells, but not on stem cells or plasma cells. Gazyva is designed to attack and destroy targeted B cells both directly and together with the body’s immune system. Chugai and Nippon Shinyaku jointly develop and market the product in Japan.

About chronic lymphocytic leukemia (CLL)
Chronic lymphocytic leukemia (CLL) a rare type of lymphoma accounting for less than one case in 100,000 population annually 2). In CLL, blood stem cells in the bone marrow become excessive abnormal lymphocytes and these abnormal cells have difficulty fighting infections. As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells, and platelets. This could result in anemia, infection, and bleeding 3). B-cell receptor signaling through BTK is one of the essential growth pathways for CLL.