On November 9, 2022 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel immunotherapies for cancer and autoimmune disease, reported the grant of two new patents (numbers 7160345 and 10-2441425) entitled "Combined Preparations for the Treatment of Cancer" by the Japanese Patent Office and South Korean Patent Office, respectively (Press release, Immutep, NOV 9, 2022, View Source [SID1234623564]).

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These new patents in Japan and South Korea were filed as divisional applications. They follow the grant of the Japanese parent patent and corresponding patents in the United States, Europe, China and Australia, as announced in 2019 through 2021.

The patents protect Immutep’s intellectual property relating to combination preparations comprising lead active immunotherapy candidate eftilagimod alpha ("efti") and a chemotherapy agent which is oxaliplatin, carboplatin, or topotecan. The combination type patent claims are written in multiple formats to maximise the scope of protection and the expiry date of both patents is 19 December 2034.

Immutep CEO Marc Voigt, commented: "We continue to invest in building a moat around efti, which is a very unique biomolecule. These new patents are notable because this family of patents protects a component of the triple combination therapy being evaluated in our INSIGHT-003 clinical trial. We also have other families of patents and patent applications which add to the protective moat around this triple combination. INSIGHT-003 is being conducted in collaboration with Professor Salah-Eddin Al-Batran and the Institute of Clinical Cancer Research IKF in Frankfurt, and importantly reports first efficacy data at SITC (Free SITC Whitepaper) 2022."

"Close alignment of our intellectual property, R&D and business development strategies continues to be a priority for the business as we push towards late-stage development and commercialisation of efti in multiple settings," he said.

About Eftilagimod Alpha (Efti)

Efti is Immutep’s proprietary soluble LAG-3 clinical stage candidate that is a first-in-class antigen presenting cell (APC) activator for the treatment of cancer, capitalising on LAG-3’s unique characteristics to stimulate both innate and adaptive immunity. Efti binds to and activates antigen presenting cells via MHC II molecules leading to expansion and proliferation of CD8+ (cytotoxic) T cells, CD4+ (helper) T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like CXCL10 that further boost the immune system’s ability to fight cancer.

Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and HER2–/HR+ metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track designation in 1st line HNSCC and in 1st line NSCLC from the United States Food and Drug Administration (FDA).

On November 9, 2022 Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, reported financial results for its fiscal first quarter ended September 30, 2022 and provided a corporate update (Press release, Kintara Therapeutics, NOV 9, 2022, View Source [SID1234623563]).

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CORPORATE HIGHLIGHTS AND RECENT DEVELOPMENTS

•Paused the REM-001 program in Cutaneous Metastatic Breast Cancer (CMBC) to conserve cash which will be used to support the funding of the Company’s ongoing international registrational study for VAL-083 in glioblastoma (GBM). By pausing the REM-001 program, the Company expects to save approximately $3.0 million through 2023 (October).
•Announced that three posters were accepted for data presentation at the 2022 Society for Neuro-Oncology (SNO) Annual Meeting. The 2022 SNO Annual Meeting will be held from November 16 through November 20, 2022 in Tampa, Florida (September).
•Received a Study May Proceed letter from the United States Food and Drug Administration to begin the Company’s 15-patient study evaluating REM-001 for the treatment of CMBC. This study was subsequently paused (August).
•Entered into a purchase agreement with Lincoln Park Capital Fund, LLC (Lincoln Park) pursuant to which Lincoln Park has committed to purchase up to $20.0 million of shares of the Company’s common stock, subject to the satisfaction of the conditions contained in the agreement as well certain limitations contained therein. As of November 8, 2022, the Company has received approximately $1.9 million in net proceeds (August).
"We have prioritized our VAL-083 program in glioblastoma patients and are looking forward to announcing top-line data in the international registrational GBM AGILE Study around the end of 2023," commented Robert E. Hoffman, Kintara’s President and Chief Executive Officer. "GBM patients and physicians are in need of additional treatments to combat this deadly disease and we believe VAL-083 may be an additional tool to help this underserved disease."

SUMMARY OF FINANCIAL RESULTS FOR FISCAL YEAR 2023 FIRST QUARTER ENDED SEPTEMBER 30, 2022

At September 30, 2022, Kintara had cash and cash equivalents of approximately $7.1 million. During the quarter ended September 30, 2022, Kintara completed the sale of common shares under a purchase agreement with Lincoln Park for net proceeds to the Company of approximately $1.9 million.

For the three months ended September 30, 2022, Kintara reported a net loss of approximately $4.6 million, or $0.07 per share, compared to a net loss of approximately $6.0 million, or $0.25 per share, for the three months ended September 30, 2021. The decreased net loss for the three months ended September 30, 2022 compared to the three months ended September 30, 2021 was largely due lower research and development as well as lower general and administrative costs.

On November 9, 2022 Aprea Therapeutics, Inc. (Nasdaq: APRE), a biopharmaceutical company focused on developing and commercializing novel synthetic lethality-based cancer therapeutics targeting DNA damage response (DDR) pathways reported financial results for the three and nine months ended September 30, 2022 and provided a business update (Press release, Aprea, NOV 9, 2022, View Source [SID1234623562]).

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"We are excited about the advancement of ATRN-119, the first macrocyclic ATR inhibitor, into clinical development," said Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea. "We look forward to collecting clinical data from our Phase 1 trial."

Third Quarter Financial Results

Cash and cash equivalents: As of September 30, 2022, the Company had $33.1 million of cash and cash equivalents compared to $53.1 million of cash and cash equivalents as of December 31, 2021. The Company believes its cash and cash equivalents as of September 30, 2022 will be sufficient to meet its current projected operating requirements through the end of 2023.
Research and Development (R&D) expenses: R&D expenses were $1.1 million for the quarter ended September 30, 2022, compared to $6.0 million for the comparable period in 2021. R&D expenses for the quarter ended September 30, 2022 primarily represented close out costs for (i) the Company’s pivotal Phase 3 clinical trial of eprenetapopt with azacitidine for the frontline treatment of TP53 mutant MDS, (ii) the Company’s Phase 2 post-transplant MDS/AML clinical trial, (iii) the Company’s Phase 1 AML trial, and (iv) the Company’s Phase 1/2 solid tumor trial and the Company’s Phase 1 dose-escalation trial of APR-548 as well as decreased non-cash stock-based compensation expense resulting from the acceleration of vesting of all outstanding stock options and restricted stock units in connection with the acquisition of Atrin in May 2022.
General and Administrative (G&A) expenses: G&A expenses were $3.1 million for the quarter ended September 30, 2022, compared to $3.4 million for the comparable period in 2021. The decrease in G&A expenses was primarily due to decreased non-cash stock-based compensation expense resulting from the acceleration of vesting of all outstanding stock options and restricted stock units in connection with the acquisition of Atrin in May 2022, offset in part by increased professional fees.
Net loss: Net loss was $4.0 million, or $0.12 per share for the quarter ended September 30, 2022, compared to a net loss of $9.5 million, or $0.45 per share for the quarter ended September 30, 2021. The Company had 52,237,885 shares of common stock outstanding as of September 30, 2022. The increased common stock outstanding resulted primarily from the conversion of 2,821,033 shares of Series A preferred stock into 28,210,330 shares of common stock during the third quarter of 2022.
Business Operations Update:

DDR Programs

ATRN-119 – ATRN-119 is an orally-bioavailable, highly potent and selective macrocyclic small molecule inhibitor of ATR, a protein with key roles in response to DNA damage. The Company is conducting a Phase 1 clinical trial to evaluate ATRN-119 monotherapy in cancer patients with defined genetic mutations. This trial was activated and opened for enrollment in the third quarter of 2022 and the Company expects to open 1-2 additional sites in the fourth quarter of 2022.

ATRN-W1051 – ATRN-W1051 is an orally-bioavailable, highly potent and selective small molecule inhibitor of WEE1, a key regulator of multiple phases of the cell cycle. ATRN-W1051 is currently in preclinical development and the Company anticipates commencing IND-enabling studies in the fourth quarter of 2022.

p53 Reactivator Programs

Eprenetapopt – APR-246, or eprenetapopt, is a small molecule p53 reactivator that has been tested in clinical trials for solid tumors and for hematologic malignancies. We currently have no ongoing clinical trials of eprenetapopt.

APR-548 – APR-548 is a second generation p53 reactivator that is being developed in an oral dosage form. We initiated a Phase 1 clinical trial testing APR-548 in relapsed/refractory MDS and AML and enrollment in the first dosing cohort was completed. There are currently no patients receiving APR-548 in this trial and enrollment into the trial has been closed.

On November 9, 2022 DiaMedica Therapeutics Inc. (Nasdaq: DMAC), a clinical-stage biopharmaceutical company focused on developing novel treatments for neurological disorders and kidney diseases, reported that financial results for the quarter ended September 30, 2022 (Press release, DiaMedica, NOV 9, 2022, View Source [SID1234623561]).

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Clinical Developments

DM199 for the Treatment of Acute Ischemic Stroke

On October 26, 2022, the Company announced that it received further guidance from the U.S. Food and Drug Administration (FDA) regarding the clinical hold on its ReMEDy2 Phase 2/3 trial. The FDA stated it is maintaining its clinical hold at this time and that additional non-clinical data related to the materials used by a hospital in the intravenous (IV) infusion process is needed to resolve the clinical hold.

In response to the FDA’s clinical hold letter in July 2022 related to three serious adverse event cases of transient acute hypotension during intravenous infusion of DM199, the Company previously submitted to the FDA supporting in vitro data that the etiology (cause) is likely related to switching the type of IV bag used in the prior ReMEDy 1 trial, where no hypotensive episodes were reported, versus the current ReMEDy 2 trial. Hypotension is a known response to DM199 treatment. Significant differences in protein binding were observed between the two types of IV bags used in the studies that the Company believes effectively altered the total amount of drug being administered. Following review of this data, the FDA requested an additional in-use in vitro stability study of the IV administration of DM199 which includes the IV tubing and mechanical infusion pump to further rule out any etiology other than IV bag protein binding.

"Preparation for the in vitro study is already underway and we are also preparing to request a Type A FDA meeting in the coming weeks to obtain additional guidance towards lifting the clinical hold and resuming the ReMEDy2 trial," commented Rick Pauls, DiaMedica’s Chief Executive Officer. "We will provide an update on the timing of completion of the in-use in-vitro study and data submission following consultation with the FDA."

The 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 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.

Balance Sheet and Cash Flow

DiaMedica reported total cash, cash equivalents and investments of $36.1 million, current liabilities of $1.5 million and working capital of $34.9 million as of September 30, 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 and investments and in working capital were due primarily to cash used to fund operating activities during the nine months ended September 30, 2022.

Net cash used in operating activities was $8.7 million and $9.4 million for the nine months ended September 30, 2022 and September 30, 2021, respectively. Cash used in operating activities is driven primarily by the Company’s net loss, partially offset by 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 $1.6 million for the three months ended September 30, 2022, down $0.7 million from $2.3 million for the three months ended September 30, 2021. R&D expenses decreased to $5.6 million for the nine months ended September 30, 2022, down $1.3 million from $6.9 million for the nine months ended September 30, 2021. The decrease for the nine-month comparison was driven primarily by reduced costs incurred during the wrap-up of the REDUX Phase 2 CKD trial and decreased non-clinical testing and manufacturing process development costs which were incurred during 2021 in preparation for initiating the Phase 2/3 ReMEDy2 trial. These decreases were partially offset by increased costs incurred in performing the Phase 2/3 ReMEDy2 trial, inclusive of costs incurred during the clinical hold, and increased personnel costs associated with expanding the Company’s R&D operations.

General and administrative (G&A) expenses were $1.5 million for the three months ended September 30, 2022, up from $1.1 million for the three months ended September 30, 2021. G&A expenses were $4.5 million for the nine months ended September 30, 2022, up from $3.5 million for the nine months ended September 30, 2021. The increase for the nine-month comparison was primarily due to increased directors’ and officers’ liability insurance, and personnel and professional services costs to support our expanding clinical programs. These increases were partially offset by a reduction in non-cash share-based compensation.

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 porcine pancreas 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 AIS and patients with chronic kidney disease. In September 2021, the FDA granted Fast Track Designation to DM199 for the treatment of AIS.

On November 9, 2022 Terns Pharmaceuticals, Inc. ("Terns" or the "Company") (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology, obesity and non-alcoholic steatohepatitis (NASH), reported financial results for the third quarter ended September 30, 2022 and corporate highlights (Press release, Terns Pharmaceuticals, NOV 9, 2022, View Source [SID1234623560]).

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"The third quarter marked an exciting period for Terns, as we continued to accelerate development of our three lead programs in indications with large unmet need. With the completion of our $65 million financing in August, we are well-positioned to advance TERN-701 in CML and TERN-601 in obesity into the clinic in the United States in 2023. We also look forward to top-line data from the Phase 2a DUET trial evaluating TERN-501 monotherapy and in combination with TERN-101, the first trial to assess both THR-β and FXR agonists in NASH, in the second half of 2023. We look forward to continued momentum in 2023 and multiple important milestones for Terns’ product candidates next year," said Sen Sundaram, chief executive officer at Terns.

Recent Developments and Anticipated Milestones

TERN-701: Oral, allosteric BCR-ABL tyrosine kinase inhibitor (TKI) for chronic myeloid leukemia

Terns intends to initiate a Phase 1 clinical trial for TERN-701 in the United States in the second half 2023 with potential interim top-line readouts from initial cohorts in 2024
TERN-701 is Terns’ proprietary, allosteric BCR-ABL TKI, designed to target the ABL myristoyl pocket, for the treatment of chronic myeloid leukemia (CML)
Allosteric TKIs, which bind to the myristoyl-binding pocket, represent a new treatment class for CML and have the potential to address active-site TKI shortcomings, including off-target activity and limited efficacy against active site resistance mutations
TERN-701 aims to address the limitations of active-site TKIs with the goal of achieving improved tumor suppression through a combination of (1) potent activity against BCR-ABL including a broad range of mutations, and (2) improved safety and tolerability profiles
Terns retains all worldwide development and commercialization rights outside of greater China
TERN-701 is out-licensed to Hansoh Pharmaceutical Group Company Limited (Hansoh) for development in the greater China region, with Hansoh responsible for all development costs in China
The Phase 1 trial in China is advancing. This trial is a dose-escalation and dose-expansion trial (NCT05367700) evaluating the tolerability, efficacy, and pharmacokinetics of TERN-701 in approximately 100 patients with CML
TERN-601: Oral, small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist for obesity

Investigational new drug (IND)-enabling activities for TERN-601, Terns’ lead GLP-1 receptor agonist program, remain on track with the goal of initiating a Phase 1 first-in-human clinical trial in obesity in 2023
The Phase 1 clinical program for TERN-601 is expected to include a single ascending dose trial and a multiple ascending dose proof-of-concept trial in obese healthy volunteers and/or people with Type 2 diabetes
Potential endpoints may include changes in body weight and glycemic control parameters
Top-line data expected in 2024
TERN-601 is Terns’ proprietary orally administered small-molecule GLP-1R agonist for the treatment of obesity
Terns has identified structures believed to be suitable for oral administration as a single agent or in combination with other drug candidates within its pipeline, including small molecule glucose-dependent insulinotropic polypeptide receptor (GIPR) modulators
TERN-501: Oral, thyroid hormone receptor-beta (THR-β) agonist for NASH

Terns presented positive data from Phase 1 clinical trial of TERN-501 in NASH at AASLD’s The Liver Meeting in November 2022
Among 24 treated participants TERN-501 was generally well tolerated and exhibited dose-dependent pharmacokinetics with low variability
TERN-501-treated participants experienced increases in sex-hormone binding globulin (SHBG), a key pharmacodynamic marker of THR-β engagement linked to decreases in levels of atherogenic lipids and NASH histologic efficacy, which were time- and dose-dependent and highly associated with TERN-501 exposure
The Phase 2a DUET trial (NCT05415722) evaluating TERN-501 monotherapy and in combination with TERN-101, the first trial assessing both THR-β and FXR agonists in NASH, remains ongoing
Primary endpoint is the relative change from baseline in liver fat content as measured by MRI protein density fat fraction (MRI-PDFF) at Week 12 for TERN-501 monotherapy compared with placebo
Secondary endpoints include assessment of changes in MRI-PDFF (combination vs. placebo) and MRI corrected T1, or cT1 (TERN-501 monotherapy vs. placebo as well as 501+101 combination vs. placebo)
Top-line data expected in the second half of 2023
TERN-501 is a THR-β agonist with high metabolic stability, enhanced liver distribution and greater selectivity for THR-β compared to other THR-β agonists in development
Pre-clinical and discovery programs: TERN-201 (VAP-1) and TERN-800 series (GIPR modulator program)

Terns is conducting pre-clinical in vivo studies exploring TERN-201, a vascular adhesion protein-1 (VAP-1) inhibitor co-administered with immune checkpoint inhibitors (e.g., anti-PD1 and anti-CTLA4 antibodies) to assess the potential for TERN-201 to enhance response rates in solid tumors
Discovery efforts are ongoing for the TERN-800 series of small molecule GIPR modulators for obesity, with the potential for combination with GLP-1 receptor agonists, such as TERN-601
Business Update

Terns closed its August 2022 underwritten offering of 12,250,000 shares of its common stock at $2.42 per share and, to certain investors in lieu of common stock, pre-funded warrants to purchase 14,630,000 shares of common stock at a price of $2.4199 per pre-funded warrant. The gross proceeds to Terns for the offering were approximately $65.0 million, before deducting underwriting discounts and commissions and other offering expenses
Terns anticipates existing cash to be sufficient to fund operations into 2025, including expected clinical trial readouts for three product candidates across three indications during that time period
Upcoming Investor Events

Terns will participate in a fireside chat at the virtual Evercore ISI HealthCONx Conference on November 30, 2022. A live webcast will be available on the investor relations page of the Terns Pharmaceuticals website at View Source A replay of the webcast will be archived on Terns’ website for 30 days following the presentation.
Third Quarter 2022 Financial Results

Cash Position: As of September 30, 2022, cash, cash equivalents and marketable securities were $187.3 million as compared with $166.0 million as of December 31, 2021. Based on its current operating plan, Terns expects these funds will be sufficient to support its planned operating expenses into 2025, including through the expected proof-of-concept clinical readouts for TERN-701, TERN-601 and TERN-501

Research and Development (R&D) Expenses: R&D expenses were $12.2 million for the quarter ended September 30, 2022, as compared with $7.2 million for the quarter ended September 30, 2021

General and Administrative (G&A) Expenses: G&A expenses were $5.1 million for the quarter ended September 30, 2022, as compared with $4.7 million for the quarter ended September 30, 2021

Net Loss: Net loss was $16.8 million for the quarter ended September 30, 2022, as compared with $11.8 million for the quarter ended September 30, 2021