On March 27, 2024 AstraZeneca reported that Truqap (capivasertib) in combination with Faslodex (fulvestrant) has been approved in Japan for the treatment of adult patients with unresectable or recurrent PIK3CA, AKT1, or PTEN-altered hormone receptor (HR)-positive, HER2-negative breast cancer following progression after treatment with endocrine therapy (Press release, AstraZeneca, MAR 27, 2024, View Source [SID1234641513]).

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The approval by the Japanese Ministry of Health, Labour, and Welfare (MHLW) was based on the results from the CAPItello-291 Phase III trial published in The New England Journal of Medicine.1 In the trial, Truqap in combination with Faslodex reduced the risk of disease progression or death by 50% versus Faslodex alone in patients with tumours harbouring PI3K/AKT pathway biomarker alterations (based on hazard ratio of 0.50, 95% confidence interval 0.38-0.65; p=<0.001; median progression-free survival (PFS) 7.3 versus 3.1 months).1

In Japan, more than 90,000 women were diagnosed with breast cancer in 2022, and more than 17,000 patients died from the disease in the same year.2 Globally, HR-positive breast cancer (expressing estrogen or progesterone receptors, or both), is the most common breast cancer subtype, with more than 65% of tumours considered HR-positive and HER2-low or HER2-negative.3 Collectively, mutations in PIK3CA, AKT1 and alterations in PTEN occur frequently, affecting approximately 50% of patients with advanced HR-positive breast cancer.4-6 Endocrine therapies are widely used in this setting, often in combination with cyclin-dependent kinase (CDK) 4/6 inhibitors, but some tumours develop resistance to these therapies, underscoring the need for additional combination approaches with endocrine therapy to extend time before the initiation of chemotherapy.7

Masakazu Toi, MD, PHD, Director of Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Japan said: "The approval of capivasertib and fulvestrant signifies a new era of care in advanced hormone receptor-positive breast cancer in Japan, providing a much-needed new treatment option for approximately half of patients in this setting who have tumours harbouring mutations in PIK3CA, AKT1 or alterations in PTEN. It is important for us to detect these specific tumour biomarker alterations in each patient we see, so that they are potentially able to benefit from this important combination to extend the effectiveness of endocrine-based treatment and delay disease progression."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said:
"Breast cancer is the most common cancer among women in Japan, and innovative, new treatment options are urgently needed. Today’s approval of Truqap, a first-in-class AKT-inhibitor, represents a significant step forward for HR-positive breast cancer treatment and an important new option for approximately fifty per cent of patients who have tumours with these specific mutations or alterations."

In the CAPItello-291 trial, the safety profile of Truqap plus Faslodex was similar to that observed in previous trials evaluating this combination.1

The MHLW have also approved a companion diagnostic test to detect the relevant alterations (PIK3CA, AKT1 and PTEN).

Regulatory applications are currently under review in China, the European Union, and several other countries, and this indication for Truqap in combination with Faslodex is already approved in the US and several other countries based on results from the CAPItello-291 trial.

Financial considerations
Following this approval in Japan, Astex Therapeutics is eligible to receive a milestone payment from AstraZeneca on first commercial sale of the drug in Japan as well as royalties on future sales in line with the agreement between the two companies.

Notes

HR-positive breast cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related death worldwide.8 More than two million patients were diagnosed with breast cancer in 2022, with more than 665,000 deaths globally.8

HR-positive breast cancer (expressing estrogen or progesterone receptors, or both), is the most common subtype of breast cancer with more than 65% of tumours considered HR-positive and HER2-low or HER2-negative.3

The growth of HR-positive breast cancer cells is often driven by estrogen receptors (ER), and endocrine therapies that target ER-driven disease are widely used as 1st-line treatment in the advanced setting, and often paired with CDK4/6 inhibitors.7,9,10 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.9 Once this occurs, treatment options are limited – with chemotherapy being the current standard of care – and survival rates are low with approximately 30% of patients anticipated to live beyond five years after diagnosis.3,9,11

The optimisation of endocrine therapy and overcoming resistance to enable patients to continue benefiting from these treatments, as well as identifying new therapies for those who are less likely to benefit, are active areas of focus for breast cancer research.

CAPItello-291
CAPItello-291 is a Phase III, double-blind, randomised trial evaluating the efficacy of Truqap in combination with Faslodex versus placebo plus Faslodex for the treatment of locally advanced (inoperable) or metastatic HR-positive, HER2-low or negative (immunohistochemistry (IHC) 0 or 1+, or IHC 2+/in-situ hybridisation (ISH)-negative) breast cancer.

The global trial enrolled 708 adult patients with histologically confirmed HR-positive, HER2-low or negative breast cancer whose disease has recurred or progressed during or after aromatase inhibitor therapy, with or without a CDK4/6 inhibitor, and up to one line of chemotherapy for advanced disease. The trial has dual primary endpoints of PFS in the overall patient population and in a population of patients whose tumours have qualifying alterations in the PI3K/AKT pathway (PIK3CA, AKT1 or PTEN genes). In the trial, approximately 40% of tumours had these alterations and approximately 70% of patients received a prior CDK4/6 inhibitor.

Truqap
Truqap is a first-in-class, potent, adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms (AKT1/2/3). Truqap 400mg is administered twice daily according to an intermittent dosing schedule of four days on and three days off. This was chosen in early phase trials based on tolerability and the degree of target inhibition.

Truqap in combination with Faslodex is approved in the US, Japan and several other countries for the treatment of adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1 or PTEN) based on the results from the CAPItello-291 trial. Eligible patients will have progressed on at least one endocrine-based regimen in the metastatic setting or experienced recurrence on or within 12 months of completing adjuvant therapy.

Truqap is currently being evaluated in Phase III trials for the treatment of multiple subtypes of breast cancer and in other tumour types in combination with established treatments. The ongoing clinical research programme is focused on tumours reliant on signalling via the PI3K/AKT pathway, and in tumours harbouring biomarker alterations in this pathway.

Truqap was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).

Faslodex
Faslodex is an endocrine therapy indicated for the treatment of estrogen receptor-positive, locally advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy, or with disease relapse on or after adjuvant anti-estrogen therapy, or disease progression on anti-estrogen therapy.

In the US, EU and Japan, Faslodex is also approved in combination with CDK4/6 inhibitors for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer, whose cancer has progressed after endocrine medicine. Faslodex represents a hormonal treatment approach that helps to slow tumour growth by blocking and degrading the estrogen receptor – a key driver of disease progression.

Faslodex is approved as monotherapy or in combination with medicines from various drug classes including CDK4/6, PI3K and AKT inhibitors for the treatment of patients with HR-positive advanced breast cancer and is being evaluated in combination with medicines from other drug classes.

On March 27, 2024 Vaccinex, Inc. (Nasdaq: VCNX) ("Vaccinex" or the "Company"), a clinical-stage biotechnology company pioneering a differentiated approach to treating Alzheimer’s disease and cancer through the inhibition of SEMA4D, reported that it has entered into definitive agreements with certain institutional investors for the purchase and sale of 193,000 shares of its common stock in a registered direct offering together with warrants to purchase up to an aggregate of 193,000 shares of common stock in a concurrent private placement priced at-the-market under Nasdaq rules at a combined purchase price of $7.77 per share and accompanying warrant (Press release, Vaccinex, MAR 27, 2024, View Source [SID1234641512]). The warrants will have an exercise price of $7.64 per share, will be immediately exercisable upon issuance and will expire 5 years from the initial exercise date. The registered direct offering and concurrent private placement are referred to herein as the "Transactions."

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The closing of the Transactions is expected to occur on or about March 28, 2024, subject to the satisfaction of customary closing conditions. The gross proceeds from the Transactions are expected to be approximately $1.5 million, before deducting financial advisory fees and other estimated expenses related to the Transactions. The Company intends to use the net proceeds from the Transactions for working capital and general corporate purposes.

The registered direct offering of the shares of common stock is being made pursuant to an effective shelf registration statement on Form S-3 (File No 333-271074) previously filed with the U.S. Securities and Exchange Commission (the "SEC"). A prospectus supplement describing the terms of the registered direct offering will be filed with the SEC and will be available on the SEC’s website located at View Source Electronic copies of the prospectus supplement may be obtained.

The Company has also agreed to sell $1.1 million and up to $1.25 million in a separate private placement of common stock together with warrants to purchase shares of the Company’s common stock at the same combined purchase price as the Transactions. The closing of this transaction is also expected to occur on or about March 28, 2024.

The private placement of the warrants and the separate private placement of common stock together with warrants are being made in reliance on an exemption from registration under Section 4(a)(2) of the Securities Act and/or Regulation D thereunder.

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

On March 27, 2024 Precision BioSciences, Inc. (Nasdaq: DTIL), an advanced gene editing company utilizing its novel proprietary ARCUS platform to develop in vivo gene editing therapies for sophisticated gene edits, including gene elimination, insertion, and excision, reported financial results for the fourth quarter and fiscal year ended December 31, 2023 and provided a business update (Press release, Precision Biosciences, MAR 27, 2024, View Source [SID1234641511]).

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"2023 was a transformative year for Precision BioSciences as we fully transitioned to our core capability as an in vivo gene editing company rapidly advancing development of our wholly owned in vivo programs led by PBGENE-HBV and quickly followed by PBGENE-PMM. As a part of this transition, we successfully monetized our prior CAR T investments and completed a $40 million public offering, strengthening our balance sheet beyond Phase 1 readouts for both wholly owned programs," said Michael Amoroso, President and Chief Executive Officer of Precision BioSciences. "We are well positioned to continue to execute against our objectives, having received regulatory feedback from the U.S. Food and Drug Administration (FDA) and key regulatory agencies outside the U.S. which provided clarity and alignment to guide our planned investigational new drug (IND) and/or clinical trial application (CTA) filings for PBGENE-HBV in 2024. In addition, our partner iECURE has advanced the first ARCUS-mediated gene editing program into the clinic, bolstering our confidence and establishing regulatory precedent for ARCUS in vivo gene editing programs with the potential to deliver a curative treatment for patients."

"As we look ahead, we continue to advance our focused strategy to differentiate ARCUS within the gene editing field and progress both our wholly owned and partnered gene editing programs. In our wholly owned pipeline, we plan to continue to advance PBGENE-HBV and PBGENE-PMM towards IND and/or CTA filings in 2024 and 2025, respectively, as well as commence a new gene insertion program of our own. More broadly, we anticipate presenting and publishing new data this year that further differentiates ARCUS as a potential best-in-class tool for high efficiency gene insertion via homology directed repair. We believe that these complementary objectives will continue to build momentum and establish Precision BioSciences as a leading in vivo gene editing company," added Mr. Amoroso.

Wholly Owned Portfolio

PBGENE-HBV (Viral Elimination Program): Precision is developing PBGENE-HBV for the treatment of patients with chronic hepatitis B. Currently, it is estimated that approximately 300 million people worldwide are afflicted with chronic Hepatitis B. In November 2023, Precision presented preclinical efficacy and safety data at the 2023 American Association for the Study of Liver Diseases Annual Meeting. The data demonstrated strong proof of concept efficacy and safety for the final clinical candidate including no detectable off-target editing at maximal on-target editing dose.

In February 2024, Precision announced that the company had received pre-IND regulatory feedback from the U.S. FDA in addition to regulatory feedback from agencies outside the U.S. providing clarity and alignment on PBGENE-HBV IND/CTA-enabling preclinical plans and clinical strategy. Precision expects to submit an IND and/or CTA for this program in 2024.

PBGENE-PMM (Mutant Mitochondrial DNA Elimination Program): PBGENE-PMM is a first of its kind potential treatment for m.3243-associated primary mitochondrial myopathy (PMM). Mitochondrial diseases are the most common hereditary metabolic disorder in the world, affecting 15,000 to 25,000 people in the U.S. alone. PMM currently lacks a curative treatment and impacts approximately 50% of patients with mitochondrial disease. In a 2023 publication in Nature Metabolism, Precision shared new pre-clinical data highlighting the high specificity of the mitoARCUS nucleases to edit and eliminate mutant mitochondrial DNA while allowing wild-type (normal) mitochondrial DNA to repopulate in the mitochondria, thus improving normal function. ARCUS nucleases are able to penetrate the mitochondrial membrane unlike CRISPR-Cas, base and prime editors because ARCUS is single component editor that does not require a guide RNA. Precision expects to submit an IND and/or CTA for this program in 2025.

Partnered Programs

iECURE-OTC (Gene Insertion Program): Led by iECURE, ECUR-506 is the first ARCUS-mediated gene editing program to advance into the clinic following approval from the Australian Therapeutic Goods Administration and the U.K. Medicines & Healthcare products Regulatory Agency (MHRA) for initiation of the OTC-HOPE study, in the first half of 2024. The OTC-HOPE study is a first-in-human Phase 1/2 trial evaluating ECUR-506 as a potential treatment for neonatal onset ornithine transcarbamylase (OTC) deficiency. Non-human primate (NHP) data presented by researchers from the University of Pennsylvania’s Gene Therapy Program demonstrated sustained gene insertion of a therapeutic OTC transgene one-year post-dosing in newborn and infant NHP’s with high efficiency.

PBGENE-NVS (Gene Insertion Program): Precision continues to advance its gene editing program with Novartis to develop a custom ARCUS nuclease for patients with hemoglobinopathies, such as sickle cell disease and beta thalassemia. The collaborative intent is to insert, in vivo, a therapeutic transgene as a potential one-time transformative treatment administered directly to the patient to overcome disparities in patient access to treatment with other therapeutic technologies, including those that are targeting an ex vivo gene editing approach.

PBGENE-DMD (Gene Excision Program): Precision continues its in vivo gene editing collaboration with Prevail Therapeutics, a wholly owned subsidiary of Eli Lilly and Company (Lilly), in applying ARCUS nucleases to three initial targets, including Duchenne muscular dystrophy (DMD) in muscle, a central nervous system directed target, and a liver directed target. The goal of the PBGENE-DMD program is to utilize a pair of ARCUS nucleases, delivered by a single adeno-associated virus (AAV), that are designed to excise an approximately 500,000 base pair mutation "hot spot" region from the dystrophin gene to generate a variant of the dystrophin protein that is functionally competent. During the Company’s September 2023 R&D Day, Precision highlighted preclinical data demonstrating the potential of ARCUS in vivo gene editing for large gene excisions and that the edited dystrophin variant was observed in multiple tissue types frequently involved in progression of DMD, including skeletal muscle, heart, and diaphragm, enabling significantly improved muscle function.

PBGENE-LLY2 (Gene Insertion Program): During the Precision 2023 Gene Editing R&D Day, Precision highlighted new data demonstrating that ARCUS is capable of high efficiency gene insertion in nondividing cells in adult nonhuman primates, the most challenging context for gene insertion. In the pre-clinical study involving coadministration of AAV and lipid nanoparticle, Precision scientists observed 40% to 45% overall gene insertion efficiency at 1- and 3-months. Precision scientists largely attribute this high efficiency to the unique ARCUS cut type which drives homology directed repair, even in nondividing cells.

Business Updates – Monetization of CAR T Investments:

Completed Licensing Deal with TG Therapeutics for Cell Therapy Azer-Cel in Autoimmune Diseases:
In January 2024, Precision announced the completion of a transaction with TG Therapeutics (Nasdaq: TGTX) for certain exclusive and non-exclusive license rights to develop Azercabtagene Zapreleucel (azer-cel) for autoimmune diseases and other indications outside of cancer. In exchange for these rights, Precision received upfront and potential near-term economics valued at $17.5 million. The upfront payment of $7.5 million consisted of cash and the purchase of 97,360 shares of Precision common stock by TG Therapeutics at a price of $23.10 per share, a 100% premium to the 30-day volume-weighted average price. Shares and per share amounts have been adjusted for Precision’s reverse stock split effective February 14, 2024. In addition, Precision will receive $2.5 million in deferred consideration due within 12 months as an equity investment in Precision’s common stock at a 100% premium to the then 30-day VWAP prior to purchase. Upon the achievement of certain near-term clinical milestones, Precision will receive an additional $7.5 million payment in cash and the purchase of Precision common stock by TG Therapeutics at a 100% premium to the then current 30-day VWAP. Precision is eligible to receive up to $288 million in additional milestone payments based on the achievement of certain clinical, regulatory, and commercial milestones, in addition to high-single-digit to low-double-digit royalties on net sales.

Completed Licensing Deal with Imugene Limited for Azer-Cel in Cancer:
The agreement with TG Therapeutics followed an agreement with Imugene Limited (ASX: IMU) in August 2023 for an exclusive license for azer-cel in cancer. In exchange for global rights to azer-cel for cancer Precision received upfront economics valued at $21 million consisting of cash and convertible notes. In addition, Precision is eligible for a potential $8 million near-term payment in cash and equity upon successful completion of the phase 1b dosing in the CAR T relapsed LBCL patient population. Precision is eligible to receive up to $198 million in additional milestone payments and double-digit royalties on net sales of azer-cel.

Completed Non-Exclusive Patent License Agreement with Caribou Biosciences:
In February 2024, Precision announced that it had granted Caribou Biosciences (Nasdaq: CRBU) a non-exclusive, worldwide license, with the right to sublicense, to one of Precision’s foundational cell therapy patent families for use with CRISPR-based therapies in the field of human therapeutics. Under the terms of the agreement, Precision received an upfront payment and, upon commercialization by Caribou, will receive royalties on net sales of licensed products. In addition, for each occurrence of certain strategic transactions involving Caribou, Precision is entitled to receive a specific tiered milestone payment.

In total, these three transactions provide Precision BioSciences with nearly $50 million in upfront payments and potential near-term cash payments which, if realized, will be invested in the in vivo gene editing programs.

Business Updates – $40 Million Offering:

On March 1, 2024, Precision completed a $40 million public underwritten offering consisting of 2,500,000 shares of its common stock and accompanying warrants to purchase up to 2,500,000 shares of common stock at a combined offering price of $16.00 price per share, for total gross proceeds of $40 million, before deducting underwriting discounts and commissions. The financing included participation from leading life sciences investors, including Perceptive Advisors, Janus Henderson Investors, Aquilo Capital Management, LLC and LYFE Capital. The capital raised in the public offering is expected to extend the company’s cash runway into the second half of 2026, fund development of our PBGENE-HBV and PBGENE-PMM in vivo gene editing programs through Phase 1 read out, and enable commencement of a new wholly owned gene insertion program.

Quarter Ended December 31, 2023 Financial Results:

Cash and Cash Equivalents: As of December 31, 2023, Precision had $116.7 million in cash and cash equivalents. The cash balance as of December 31, 2023 does not include the benefit of cash received from TG Therapeutics, Caribou or the $40 million capital raise since year-end. Upfront and potential near-term cash from CAR T transactions, cash received from the public offering, along with existing cash and cash equivalents, expected operational receipts, continued fiscal and operating discipline, availability of Precision’s at-the-market (ATM) facility, and available credit are expected to extend Precision’s cash runway into the second half of 2026.

Revenues: Total revenues for the quarter ended December 31, 2023 were $7.0 million, as compared to $10.6 million for the quarter ended December 31, 2022. The decrease of $3.6 million in revenue during the quarter ended December 31, 2023 was primarily the result of a decrease in revenue recognized from collaborations.

Research and Development Expenses: Research and development expenses were $13.4 million for the quarter ended December 31, 2023, as compared to $12.7 million for the quarter ended December 31, 2022. The increase of $0.7 million was primarily due to an increase in PBGENE-HBV and PBGENE-PMM program costs as the programs continue to advance toward the clinic.

General and Administrative Expenses: General and administrative expenses were $8.5 million for the quarter ended December 31, 2023, as compared to $10.0 million for the quarter ended December 31, 2022. The decrease of $1.5 million was primarily due to operational discipline, a decrease in the number of employees and a decrease in share-based compensation expense.

Other Income and Expense: Total other income was $1.5 million for the quarter ended December 31, 2023, as compared to total other expense of $7.3 million for the quarter ended December 31, 2022. The increase was primarily driven by an impairment related to the iECURE PCSK9 collaboration in the quarter ended December 31, 2022, and a gain in fair value of equity investment in iECURE in the quarter ended December 31, 2023, partially offset by a loss from equity method investments.

Continuing Operations: Loss from continuing operations was $13.4 million for the quarter ended December 31, 2023, as compared to $19.4 million for the quarter ended December 31, 2022.

Net Loss: Net loss was $16.3 million, or $(4.06) per share (basic and diluted), including a $2.9 million loss from discontinued operations for the quarter ended December 31, 2023. Net loss was $28.5 million, or $(7.70) per share (basic and diluted), including a $9.1 million loss from discontinued operations for the quarter ended December 31, 2022. Discontinued operations represent costs associated with the development of allogeneic CAR T immunotherapies.

Fiscal Year 2023 Financial Results:

Revenues: Total revenues for the year ended December 31, 2023 were $48.7 million, as compared to $25.1 million for the year ended December 31, 2022. The increase of $23.6 million in revenue during the year ended December 31, 2023 was primarily the result of an increase in revenue recognized under the Prevail and Novartis agreements.

Research and Development Expenses: Research and development expenses were $53.4 million for the year ended December 31, 2023, as compared to $46.1 million for the year ended December 31, 2022. The increase of $7.3 million was primarily due to an increase in PBGENE-HBV and PBGENE-PMM program costs as the programs continue to advance toward the clinic in addition to increases in outsourced research and development costs primarily related to consulting fees, employee-related costs, and facility-related costs.

General and Administrative Expenses: General and administrative expenses were $39.1 million for the year ended December 31, 2023, as compared to $41.3 million for the year ended December 31, 2022. The decrease of $2.2 million was a result of operational discipline, lower headcount, and decreases in share-based compensation expense.

Other Income and Expense: Total other income was $1.2 million for the year ended December 31, 2023, as compared to total other expense of $10.6 million for the year ended December 31, 2022. The increase was primarily driven by an impairment related to the iECURE PCSK9 collaboration in the year ended December 31, 2022, an increase in interest income, and an increase in the loss from equity method investments.

Continuing Operations: Loss from continuing operations was $42.5 million for the year ended December 31, 2023, as compared to $72.9 million for the year ended December 31, 2022.

Net Loss: Net loss was $61.3 million, or $(15.96) per share (basic and diluted), including a $18.8 million loss from discontinued operations for the year ended December 31, 2023. Net loss was $111.6 million, or $(38.10) per share (basic and diluted), including a $38.7 million loss from discontinued operations for the year ended December 31, 2022. Discontinued operations represent costs associated with the development of allogeneic CAR T immunotherapies.

On March 27, 2024 PDS Biotechnology Corporation (Nasdaq: PDSB) (PDS Biotech or the Company), a late-stage immunotherapy company focused on transforming how the immune system targets and kills cancers and the development of infectious disease vaccines, reported an update to its clinical development strategy and reported its financial results for the year ended December 31, 2023 (Press release, PDS Biotechnology, MAR 27, 2024, View Source [SID1234641510]).

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"We have obtained compelling data from several Phase 2 trials in the fourth quarter of 2023, including long-term survival data from the National Cancer Institute (NCI)-led triple combination trial of PDS01ADC in combination with Versamune HPV (PDS0101) and an investigational immune checkpoint inhibitor (ICI), as well as our VERSATILE-002 study," said Frank Bedu-Addo, PhD, President and Chief Executive Officer of PDS Biotech. "We now have a better understanding of how our drug platform technology works in advanced cancer, and we have therefore made the strategic, data-driven decision to add our novel, investigational IL-12 fused antibody drug conjugate, PDS01ADC, to the promising combination of Versamune HPV and KEYTRUDA to advance the triple combination as our top clinical development priority."

"By initially addressing the rapidly growing unmet medical need in recurrent metastatic HPV+ head and neck squamous cell cancer (HNSCC), we strongly believe this approach may rapidly establish our proprietary combination of PDS01ADC and Versamune HPV as a transformative oncology treatment. The data suggest that the triple combination may result in a significant improvement in overall survival rates for patients who currently lack an effective treatment option. It may also significantly increase the rates of durable tumor shrinkage or overall responses," said Dr. Bedu-Addo. "We are grateful to the patients and physicians who participated in the clinical trials which have helped inform our understanding of how the drug therapies may be used most effectively to safely address advanced cancer, and our decision to prioritize the triple combination."

With the recent long-term survival Phase 2 data from the NCI-led triple combination trial, together with favorable safety and extended survival results seen in both ICI naïve and resistant patients in our VERSATILE-002 trial, PDS Biotech has decided to prioritize the triple combination in place of the VERSATILE-003 trial. This decision enables PDS Biotech to focus its resources on the drug regimen it believes has the highest potential to benefit patients with HNSCC and to drive shareholder value.

"We have had several discussions with key opinion leaders in HNSCC regarding the use of the triple combination in HNSCC. A clear unmet need is seen in HPV+ HNSCC with few agents being studied in this population due to the difficulty in treating advanced HNSCC," said Kirk V. Shepard, M.D., Chief Medical Officer of PDS Biotech. "These discussions with expert HNSCC oncologists have guided our decision to prioritize the triple combination in our efforts to address the growing incidence of advanced HPV+ HNSCC."

"Despite good outcomes in many patients with HPV-related HNSCC, approximately 20% of patients will develop recurrent, incurable disease, often in young individuals in the prime of their lives. HPV-related HNSCC that progresses after standard first-line chemotherapy is a devastating, hard-to-treat cancer with no HPV-related treatment currently approved. The NCI clinical trial data show significant promise in the use of PDS01ADC in combination with Versamune HPV," said Katharine A. Price, M.D., Associate Professor of Oncology, Head and Neck Disease Group, Mayo Clinic Comprehensive Cancer Center and Principal Investigator of PDS Biotech’s upcoming triple combination trial. "A controlled randomized clinical trial that builds upon the current data is warranted, and I am intrigued by the potential of this unique combination to treat HNSCC."

Clinical Strategy Update

Triple Combination Clinical Trial (PDS01ADC, Versamune HPV and KEYTRUDA)

•
Company in discussions with the U.S. Food and Drug Administration (FDA) on the design of potentially pivotal clinical trial to treat HPV+ HNSCC, with the trial expected to start in 2024.

•
Previously announced data from Phase 2 NCI-led triple combination clinical trial for the treatment of recurrent/metastatic ICI naïve and ICI resistant HPV16-positive cancers including head and neck, anal, cervical, vaginal and vulvar cancers support rationale:

•
ICI naïve group: 75% of patients remain alive at 36 months. The median OS was not reached. Published results show a 36-month survival rate of approximately 20% with ICIs. ORR of 75% and complete response of 38% were seen in patients treated with the triple combination. Published ORR of <40% seen with immunotherapeutic agents.

•
ICI resistant group: 12-month overall survival (OS) rate of 72%, and 63% overall response rate (ORR) in patients with optimal dose of PDS01ADC. Median OS approximately 20 months; published 12-month OS rate in HPV-positive ICI-resistant cancer is ~30%; published median OS in HPV-positive ICI-resistant cancer is 3.4 months.

•
Responses were seen in all HPV-positive tumor types.

Leadership Appointments

•
In January 2024, announced the appointment of Dr. Shepard as Chief Medical Officer.

•
In November 2023, announced the appointment of Lars Boesgaard as Chief Financial Officer.

Full Year 2023 Financial Results

Net loss for the year ended December 31, 2023, was approximately $42.9 million, or $1.39 per basic and diluted share, compared to a net loss of $40.9 million, or $1.43 per basic share and diluted share, for the year ended December 31, 2022. The higher net loss was primarily the result of increased operating loss and increased net interest expense.

Research and development expenses for the year ended December 31, 2023, decreased to $27.8 million, compared to $29.4 million for the year ended December 31, 2022. The decrease of $1.7 million was primarily attributable to the $10 million purchase of the rights to PDS01ADC in 2022, partially offset by an increase in clinical costs of $6.1 million and an increase in personnel costs of $2.1 million.

General and administrative expenses for the year ended December 31, 2023, increased to $15.3 million compared to $12.2 million for the year ended December 31, 2022. The $3.1 million increase was primarily attributable to an increase in personnel costs of $1.5 million and an increase in professional fees of $1.6 million.

Total operating expenses for the year ended December 31, 2023, were $43.0 million, an increase of approximately 3.3% compared to $41.7 million total operating expenses for the year ended December 31, 2022.

Net interest expense increased to $1.3 million for the year ended December 31, 2023, compared to $0.4 million for the year ended December 31, 2022. The change was due to higher interest expense related to the Company’s notes payable, partially offset by higher interest income on bank deposits.

During the fourth quarter of 2023, the Company raised approximately $10.5 million in net proceeds from its "at-the-market" sales agreement.

The Company’s cash balance as of December 31, 2023, was $56.6 million.

Conference Call and Webcast
The conference call is scheduled to begin at 8:00 AM ET today, March 27, 2024. Participants should dial 877-704-4453 (United States) or 201-389-0920 (International) and reference conference ID 13745320. To access the webcast, please use the following link. The event will be archived on the Investor Relations section of PDS Biotech’s website for six months.

On March 27, 2024 Moleculin Biotech, Inc., (Nasdaq: MBRX) (Moleculin or the Company), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported it has received an Issue Notification from the United States Patent and Trademark Office (USPTO) for U.S. Patent number 11,951,118 titled, "Preparation of Preliposomal Annamycin Lyophilizate" (the ‘118 patent’) to be issued on April 9, 2024 to Moleculin and The University of Texas System Board of Regents (Press release, Moleculin, MAR 27, 2024, View Source [SID1234641508]).

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When issued, the patent will provide claims to compositions that contain Annamycin with a base patent term extending until June 2040, subject to extension to account for time required to fulfill regulatory requirements for FDA approval. Moleculin’s novel candidate for the treatment of acute myeloid leukemia (AML) and soft tissue sarcoma lung metastases (STS lung mets) uses a unique lipid-based delivery technology. In addition to the expected ‘118 patent, Moleculin has additional patent applications pending in the U.S. and in major jurisdictions worldwide.

Walter Klemp, CEO and Chairman of Moleculin, stated, "We believe this critical milestone is very well timed, as it removes a major risk element in the overall assessment of the potential asset value for Annamycin just in time for the potential partnering discussions which we expect to have in the near future. Especially in light of our recent announcement that Annamycin has delivered a 60% CRc (complete response composite) rate in 2nd line AML subjects, outperforming the pivotal trial CRc rate of every other drug approved in this 2nd line space by a wide margin. Issuance of this patent underscores the importance and proprietary nature of the innovation that makes this next generation anthracycline possible."

Annamycin is Moleculin’s next-generation anthracycline, initially expected to fulfill a significant unmet need for the 2nd line treatment of relapsed or refractory AML patients. For a description of the magnitude of this opportunity, please see the Company’s video at this link. As described in the Company’s latest corporate update, Annamycin’s recent performance in a Phase 1B/2 clinical trial produced patient response data multiple times greater than the response rates used for the approval of all existing AML drugs approved for 2nd line treatment. Servier acquired two 2nd line AML drugs with lower pivotal clinical trial performance data with a valuation in excess of $1.8 billion.

Disclosure

MD Anderson has an institutional conflict of interest with Moleculin, and this relationship is managed according to an MD Anderson Institutional Conflict of Interest Management and Monitoring Plan.