On May 10, 2023 INOVIO (NASDAQ:INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, reported financial results and operational highlights for the first quarter of 2023 (Press release, Inovio, MAY 10, 2023, View Source [SID1234631379]). INOVIO’s management will host its quarterly conference call and webcast today at 4:30 p.m. EDT. The live webcast and replay may be accessed by visiting INOVIO’s website at View Source

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"In the first quarter of 2023 we made solid progress with several key pipeline candidates, including important headway in our development plans for INO-3107, our DNA medicine candidate for the treatment of RRP," said INOVIO’s President and Chief Executive Officer, Dr. Jacqueline Shea. "From our ongoing discussions, we believe we are in alignment with the FDA on several critical design elements for our planned Phase 3 program for INO-3107, as we continue to work through a number of their questions. Additionally, we were also encouraged to receive a positive opinion from the European Committee for Orphan Medicinal Products on our application for orphan drug designation for INO-3107. The final determination is now with the European Commission, which will decide on our application this month. We believe the committee’s opinion is another step in the right direction for the development of this candidate on a global basis."

Dr. Shea continued: "Since our last quarterly report, INOVIO has presented at several scientific and medical conferences, including presentations by lead investigators from our RRP and Ebola booster studies sharing important new immunological and safety data that shows the immense potential and versatility of our candidates. At the same time, we continued our focus on operational excellence, taking steps to build upon the strong team we have in place by the hiring of Dr. Cheryl Elder as Senior Vice President of Regulatory Affairs. Cheryl’s considerable regulatory expertise and track record of successfully bringing products through licensure will help us implement efficient regulatory strategies as we work to advance our promising candidates through development and the regulatory approval process."

Organizational and Clinical Highlights

INO-3107 – Recurrent Respiratory Papillomatosis (RRP)

During the quarter, INOVIO announced data from the second cohort of its Phase 1/2 clinical trial (NCT:04398433) that was statistically significant and showed 10 of the 11 (91%) patients saw a reduction in surgical interventions in the year following initial treatment, with measurement beginning at Day 0, the start of trial therapy. Of these 10 patients, four did not require surgery. There was a statistically significant median decrease of three surgical interventions when comparing the year following treatment to the year prior. In the year prior to treatment, the number of surgical interventions for these 11 patients ranged between 2 and 8, and the median was 5. INO-3107 was well-tolerated and immunogenic among patients in the second cohort. The safety and efficacy results for the second cohort were consistent with results announced for the first cohort in October 2022.
Following quarter end, data from the entire study, including new combined safety and immunology data not previously announced, were presented by lead investigator Dr. Ted Mau at the scientific program of the American Broncho-Esophagological Association (ABEA) at the Combined Otolaryngology Spring Meetings (COSM) in Boston, Massachusetts. The presentation highlighted the safety profile of INO-3107, which continued to be well-tolerated and elicited mostly low-grade (Grade 1) treatment-emergent adverse effects (TEAEs) such as injection site pain and fatigue. There were no high-grade TEAEs deemed related to treatment and no TEAEs leading to treatment discontinuation. The new data also showed that INO-3107 provoked a strong immune response, inducing activated CD4 T cells and activated CD8 T cells with lytic potential. T-cell responses were also observed at Week 52, indicating a persistent cellular memory response. Additional analyses are ongoing to determine a possible relationship between specific CD4 and CD8 phenotypes and clinical outcomes. The new data also included a marked improvement after treatment in the RRP staging assessment score. We believe these encouraging data indicate that INO-3107 could provide clinical benefit to adults with RRP.
Following quarter end, INOVIO announced that the European Committee for Orphan Medicinal Products issued a positive opinion on INOVIO’s application for orphan drug designation for INO-3107, with the final decision from the European Commission expected in late May.
INO-4201 – Ebola Booster for ERVEBO

During the quarter, INOVIO announced positive results from a Phase 1b trial with INO-4201 as a potential Ebola booster for ERVEBO (NCT04906629) showing INO-4201 was well-tolerated and boosted humoral responses in 36 of 36 (100%) of treated participants.
Following quarter end, lead investigator Dr. Angela Huttner presented new safety and immunology data from the trial at the 33rd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in April. The new data showed that a single-dose of INO-4201 followed by electroporation was well-tolerated and immunogenic compared to placebo in a cohort of healthy volunteers primed with ERVEBO up to 5 to 7 years previously. Binding antibody titers rose significantly after boost for each time point measured, peaking at week 2 in all treated participants. Mean neutralizing antibody titers also rose and remained high and constant until the end of the 24-week trial period. There was also a noteworthy engagement of T cells, including increased production of IFNγ, IL2, and/or TNFα from EBOV-specific CD4+ and CD8+ T cells. The additional data indicated that a booster dose of INO-4201 has the potential to restore the levels of antibodies needed to extend protection against Ebola and thus could be an important tool in future Ebola outbreaks.
VGX-3100 – High-Grade Squamous Intraepithelial Lesions (HSIL)

During the quarter, INOVIO shared topline results from REVEAL2, the second Phase 3 trial for VGX-3100 as a treatment for cervical HSIL indicating that the trial results did not meet the primary endpoint in the biomarker-selected population, but the trial did achieve statistical significance in the all-participants population.
INOVIO has continued to analyze the clinical characteristics of the biomarker positive population that may have had an impact on response to treatment, such as stage of disease, infection with other HPV types, clinical site location, age, and smoking status. Additionally, INOVIO is working to better understand why some patients who exhibited a clinical response were not positive for the biomarker. INOVIO expects to share findings from its ongoing biomarker analysis in the third quarter.
In the all-participants population of REVEAL2, VGX-3100 showed an ability to clear HPV infection, with viral clearance of 37.3% in the treated group versus 8.7% in the placebo group. INOVIO continues to evaluate how this data further informs its extensive body of evidence regarding the potential of DNA medicines to treat HPV-related diseases, including anal HSIL, which can be a precursor to anal cancer. INOVIO continues to discuss next steps for developing VGX-3100 for anal HSIL with key opinion leaders and regulators.
Discussions with partner ApolloBio to support continued development of VGX-3100 in China are underway.
Strengthened Product Development Team

Dr. Cheryl Elder joined INOVIO as Senior Vice President of Regulatory Affairs, adding additional leadership and expertise to an already strong product development team. With over 30 years of experience leading cross-functional teams in drug development in multiple therapeutic areas, Dr. Elder has a successful track record of driving regulatory strategies within both small and multinational biotechnology companies, including Hoffman La Roche and, most recently, Novartis Pharmaceuticals. She will be responsible for developing INOVIO’s regulatory strategy and will lead company interaction with regulatory authorities globally.
Data Presentations & Publications

During and following the quarter, INOVIO presented, published, or submitted data from several of its clinical programs:

Glioblastoma Drug Development Summit (March): Dr. Jeffrey Skolnik, INOVIO’s Senior Vice President, Clinical Development, presented data on INO-5401 (glioblastoma therapeutic candidate).
World Vaccines Congress (April): Dr. Michael Sumner, INOVIO’s Chief Medical Officer, presented data on INO-3107 (RRP product candidate) and INO-4201 (Ebola vaccine booster candidate).
33rd European Congress of Clinical Microbiology and Infectious Diseases (April): Dr. Angela Huttner, Infectious Disease Consultant, Geneva University Hospitals, and lead investigator for the trial, presented data on INO-4201 (Ebola vaccine booster candidate).
The Laryngoscope(April): Paper entitled "Interim Results of a Phase 1/2 Open-Label Study of INO-3107 for HPV-6 and/or HPV-11–Associated RRP" accepted for publication in this peer-reviewed journal focused on advances in the diagnosis and treatment of head and neck disorders.
American Broncho-Esophagological Association Meeting (May): Dr. Ted Mau, lead investigator and laryngologist at University of Texas Southwestern Medical Center, presented data on INO-3107 (RRP therapeutic candidate).
INOVIO plans to continue to submit papers and abstracts related to its research for publication and presentation as data becomes available to various journals and medical conferences. Further details will be shared upon acceptance for publication.

First Quarter 2023 Financial Results

INOVIO reported total revenue of $115,000 for the three months ended March 31, 2023, compared to $199,000 for the same period in 2022. Total operating expenses were $44.1 million compared to $71.9 million for the same period in 2022.
INOVIO’s net loss for the quarter ended March 31, 2023 was $40.6 million, or $0.16 per basic and diluted share, compared to net loss of $79.1 million, or $0.36 per basic and diluted share, for the quarter ended March 31, 2022.
Operating Expenses

Research and development (R&D) expenses for the three months ended March 31, 2023, were $30.2 million compared to $56.0 million for the same period in 2022. The decrease in R&D expenses was primarily the result of lower drug manufacturing, clinical trial expenses and outside services related to INO-4800, and lower expensed inventory and outside services related to our CELLECTRA 3PSP device and array automation project, among other variances.
General and administrative (G&A) expenses were $13.9 million for the three months ended March 31, 2023, compared to $16.0 million for the same period in 2022. The decrease in G&A expenses was primarily related to a decrease in non-cash stock-based compensation, insurance and other outside services expenses, offset by higher legal expenses, among other variances.
Capital Resources

As of March 31, 2023, cash and cash equivalents and short-term investments were $223.8 million compared to $253.0 million as of December 31, 2022. As of March 31, 2023, the Company had 262.7 million common shares outstanding and 283.2 million common shares outstanding on a fully diluted basis, after giving effect to the exercise, vesting and conversion, as applicable, of its outstanding options, restricted stock units, convertible preferred stock, and convertible debt.
INOVIO’s balance sheet and statement of operations are provided below. Additional information is included in INOVIO’s quarterly report on Form 10-Q for the quarter ended March 31, 2023, which can be accessed at: View Source
Cash Guidance

INOVIO continues to expect its cash runway to extend into the first quarter of 2025. This projection includes a cash burn estimate of approximately $33 million for the second quarter 2023 and its ongoing expectation that cash burn will decrease incrementally from there into the first quarter of 2025. These projections do not include any funds that may be raised through the Company’s existing at-the-market program or other capital-raising activities.
Conference Call / Webcast Information

INOVIO’s management will host its quarterly conference call and webcast at 4:30 p.m. ET today. A replay of the conference call will be available following the conclusion of the call. The live webcast and replay may be accessed by visiting INOVIO’s website at View Source

On May 10, 2023 Immunocore Holdings plc (Nasdaq: IMCR), a commercial-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, infectious diseases and autoimmune conditions, reported its financial results for the first quarter ended March 31, 2023, and provided a business update (Press release, Immunocore, MAY 10, 2023, View Source [SID1234631378]).

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"In the first year of launch, we have established KIMMTRAK as the most prescribed medicine for HLA-A*02:01 positive patients with mUM in the US, Germany and France," commented Ralph Torbay, Head of Commercial of Immunocore. "We continue to work with health authorities and healthcare professionals to bring KIMMTRAK to more patients with mUM around the world, with the goal of extending their lives."

First Quarter 2023 Highlights (including post-period)

KIMMTRAK (tebentafusp-tebn) for metastatic uveal melanoma (mUM)

KIMMTRAK is approved in over 30 countries globally and commercial expansion continues as we prepare to make the medicine available to even more patients. Total net product revenue (or "net sales") arising from the sale of KIMMTRAK (tebentafusp) was £42.1 million (or $52.0 million) for the first quarter of 2023, of which £29.5 million (or $36.5 million) was in the United States, £12.3 million (or $15.2 million) in Europe, and £0.2 million (or $0.2 million) in international regions.

During the first quarter of 2023, KIMMTRAK became the most prescribed medicine for HLA*02:01 positive patients with mUM with over half of patients in first line (1L) receiving KIMMTRAK. In addition, the majority of mUM patients in the U.S. were being treated with KIMMTRAK in the community setting.

In France and Germany, an estimated 80% and 70%, respectively, of first line HLA-A*02:01 positive patients with mUM treated in the first quarter received KIMMTRAK. The Company launched KIMMTRAK in Austria and Israel in the first quarter and expects the commercial transition in Italy in the second quarter of this year. The Company expects to launch KIMMTRAK in four additional European countries by the end of 2023.

In April, the Company presented data in HLA-A*02:01+ patients with mUM at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. The data demonstrated a correlation between early circulating tumor DNA (ctDNA) reduction and longer overall survival (OS) in the Phase 3 trial with KIMMTRAK (tebentafusp). ctDNA reduction by week 9 was observed in 88% of first-line mUM patients (Phase 3 trial) and 71% in previously treated patients (Phase 2 trial). ctDNA clearance was also higher in first-line patients (37%) compared to second-line patients (13%). In both trials, this reduction was associated with longer OS. The Company presented additional data with tebentafusp including a final analysis, at almost 4 years of follow-up, from the Phase 2 trial, tumor response in orbital lesions, and in vitro data assessing direct and indirect mechanisms of tumor control from TCR-CD3 bispecifics in melanoma.

The Company had two abstracts accepted for poster presentation at the upcoming 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 2-6, 2023 in Chicago, IL:

Title: Early ctDNA reduction may identify patients with stable disease and long OS on tebentafusp

Presenting author: Dan Feng
Session: Melanoma/Skin cancers
Date & time: 3 June – 1:15-4:15 p.m. CT

Title: A Phase 2/3 trial in progress on tebentafusp as monotherapy and in combination with pembrolizumab in HLA-A*02:01+ patients with previously treated advanced non-uveal melanoma (TEBE-AM)

Presenting author: Diwakar Davar
Session: Melanoma/Skin cancers (Trial in Progress)
Date & time: 3 June – 1:15-4:15 p.m. CT

Tebentafusp Phase 2 / 3 trial in advanced melanoma

The Company has started randomizing in its Phase 2/3 clinical trial of tebentafusp in patients with previously treated advanced melanoma. The trial is randomizing patients with advanced melanoma, excluding uveal melanoma, who have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a BRAF kinase inhibitor. Patients will be randomized to one of three arms including tebentafusp, as monotherapy or in combination with an anti-PD1, and a control arm. The Phase 2 portion of the trial will include 40 patients per arm and has a dual primary endpoint of overall survival (OS) and ctDNA reduction.

IMC-F106C targeting PRAME-A02 in multiple solid tumors

The Company is continuing to expand the clinical trial footprint for PRAME-A02 trial enrolling patients into the Phase 1/2 monotherapy and combination arms across multiple tumor types, including the four expansion arms for patients with advanced ovarian, non-small cell lung, endometrial, and melanoma cancers. The Company expects to report data from the monotherapy and combination arms by the first half of 2024.

Expansion of PRAME franchise: IMC-T119C (PRAME-A24) & IMC-P115C (PRAME-A02 HLE)

In January 2023, the Company revealed the addition of two new PRAME ImmTAC candidates IMC-T119C (PRAME-A24) and IMC-P115C (PRAME-A02 HLE) for solid tumors to the pipeline. The Company plans to submit investigational new drug applications (INDs) or clinical trial applications (CTAs) for these two ImmTAC candidates in 2024.

First-in-class ImmTAC candidate – IMC-R117C (PIWIL1)

In January 2023, the Company announced the addition of IMC-R117C to the pipeline, an ImmTAC targeting a novel protein for colorectal and other gastrointestinal cancers. The Company believes IMC-R117C is the first PIWIL1 targeted immunotherapy and plans to submit an IND / CTA in the fourth quarter of 2023.

IMC-M113V: aiming for a functional cure for HIV

In February 2023, the Company presented initial safety and pharmacodynamic activity data with IMC-M113V, the first soluble TCR therapy for people living with Human Immunodeficiency Virus (HIV), at the 2023 Conference on Retroviruses and Opportunistic Infections (CROI). Five out of the ten participants who received the 15-mcg dose showed a >4-fold rise in IL6, which had been prespecified as indicative of pharmacodynamic activity based on the Company’s experience in oncology clinical trials with ImmTAC therapies.

The Company has started enrolling people living with HIV in the multiple ascending dose (MAD) part of the trial, to identify a safe and tolerable dosing schedule. This study will also test whether IMC-M113V could lead to reduction in the viral load and, after stopping all therapies (antiretroviral therapies and ImmTAV), delay or prevent HIV rebound (known as functional cure). The MAD trial will enroll up to 28 participants.

Financial Results

Total net product revenue arising from the sale of KIMMTRAK was £42.1 million (or $52.0 million) for the three months ended March 31, 2023 of which £29.5 million ($36.5 million) was in the United States, £12.3 million ($15.2 million) in Europe and £0.2 million ($0.2 million) in international region. For the three months ended March 31, 2022, we recorded revenue from the sale of KIMMTRAK and tebentafusp of £10.5 million in our first quarter of commercial launch.

The KIMMTRAK revenue of £42.1 million ($52.0 million) for the three months ended March 31, 2023 was at a similar level to the three months ended December 31, 2022, where we reported KIMMTRAK and tebentafusp revenue of £42.3 million.

For the three months ended March 31, 2023, our research and development expenses increased to £28.4 million (or $35.2 million) as compared to £18.6 million for the three months ended March 31, 2022 due to increases in expenditure on our PRAME franchise and other programs. For the three months ended March 31, 2023, our selling and administrative expenses increased to £33.3 million (or $41.2 million) from £20.1 million for the three months ended March 31, 2022 due to foreign exchange movements and increases in selling, commercial and employee costs.

Total operating loss for the three months ended March 31, 2023, was £17.4 million (or $21.5 million), compared to an operating loss of £16.5 million for the three months ended March 31, 2022.

Basic and diluted loss per share for the three months ended March 31, 2023, was £0.35 (or $0.43) compared to a basic and diluted loss per share of £0.37 for the three months ended March 31, 2022.

Cash and cash equivalents increased to £337.5 million (or $417.4 million) as of March 31, 2023 compared to £332.5 million as of December 31, 2022.

We maintain our books and records in pounds sterling. For the convenience of the reader, we have translated pound sterling amounts as of and for the period ended March 31, 2023 into U.S. dollars at a rate of £1.00 to $1.2369.

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About Uveal Melanoma

Uveal melanoma is a rare and aggressive form of melanoma, which affects the eye. Although it is the most common primary intraocular malignancy in adults, the diagnosis is rare, and up to 50% of people with uveal melanoma will eventually develop metastatic disease. Unresectable or metastatic uveal melanoma typically has a poor prognosis and had no approved treatment until KIMMTRAK.

About KIMMTRAK

KIMMTRAK is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. KIMMTRAK specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect and activate T cells to recognize and kill tumor cells. KIMMTRAK has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom.

IMPORTANT SAFETY INFORMATION

Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. CRS occurred in 89% of patients who received KIMMTRAK with 0.8% being grade 3 or 4. Ensure immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK. Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy. Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS.

Skin Reactions

Skin reactions, including rash, pruritus, and cutaneous edema occurred in 91% of patients treated with KIMMTRAK. Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions.

Elevated Liver Enzymes

Elevations in liver enzymes occurred in 65% of patients treated with KIMMTRAK. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity.

Embryo-Fetal Toxicity

KIMMTRAK may cause fetal harm. Advise pregnant patients of potential risk to the fetus and patients of reproductive potential to use effective contraception during treatment with KIMMTRAK and 1 week after the last dose.

The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate.

For more information, please see full Summary of Product Characteristics (SmPC) or full U.S. Prescribing Information (including BOXED WARNING for CRS).

About KIMMTRAKConnect

Immunocore is committed to helping patients who need KIMMTRAK obtain access via our KIMMTRAKConnect program. The program provides services with dedicated nurse case managers who provide personalized support, including educational resources, financial assistance, and site of care coordination. To learn more, visit KIMMTRAKConnect.com or call 844-775-2273.

On May 10, 2023 HTG Molecular Diagnostics, Inc. (Nasdaq: HTGM) (HTG), a platform-based life science tools and drug discovery company, reported its financial results for the quarter ended March 31, 2023 and provided recent drug discovery business highlights (Press release, HTG Molecular Diagnostics, MAY 10, 2023, View Source [SID1234631377]).

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HTG has pioneered a proprietary platform-based approach that is designed to help improve drug discovery, referred to as transcriptome-informed drug discovery and design. At the center of this approach is the application of HTG’s proprietary RNA profiling technologies, functionally married with advanced medicinal chemistry using a novel artificial intelligence ("AI")-driven platform. This unique drug candidate optimization platform is expected to allow for more biologically-relevant insight into drug candidate selection and design much earlier in the discovery process than in traditional drug discovery. HTG believes this approach will result in higher efficiency, improved risk management and cost efficiencies to bring novel drug candidate molecules from very early discovery through entry to development.

HTG achieved three significant drug discovery business milestones in the first quarter of 2023 to advance the compounds for its first target and indication through lead optimization and to further strengthen its AI-driven drug discovery engine.

First, HTG achieved in vitro demonstration of efficacy of its first lead compounds both as a standalone therapy and in combination with the current standard of care.

The Company utilized its proprietary HTG EdgeSeq RNA profiling platform to biologically interrogate the lead molecules. This data, along with other primary and secondary data, was then introduced into the Company’s AI-driven drug discovery engine, resulting in the creation of a second generation of molecules. The second generation of molecules has been subjected to the same in vitro experiments as the first, demonstrating improved efficacy over the first generation of molecules. These results also demonstrate the utility of the AI-driven drug discovery engine in combination with high-quality full transcriptome data.

Finally, the Company’s AI-driven drug discovery engine was used to design compounds using transcriptomic data as the starting point. These system-designed compounds showed highly similar characteristics to HTG’s lead compounds that were designed starting with the target. These results demonstrate the ability of HTG’s engine to design novel compounds based on transcriptomic data alone, which the Company believes will provide other opportunities for expanded platform applications, including drug repurposing.

In addition to further advancing the Company’s drug discovery platform, these first quarter efforts have significantly advanced HTG’s first oncology indication in liquid tumors through lead optimization studies and the Company expects that these efforts will support entry into preclinical development in the next several months. In addition, the Company’s second target for the treatment of solid tumors has been selected and added to HTG’s oncology portfolio, which also includes an early pipeline in neurodegenerative diseases.

"Through the diligent efforts of our strong and knowledgeable team, we have once again achieved extensive progress toward our strategy to establish our transcriptome-informed drug discovery process as the preferred methodology for small molecule drug discovery, complementing and expanding the advanced capabilities that our HTG EdgeSeq technology has provided for many years in profiling. The three major milestones reached by our team during the first quarter of 2023 have not only advanced and strengthened our AI-driven drug discovery engine, but have significantly advanced candidate molecules through lead optimization for our first indication in liquid tumors, with a program in solid tumors expected to follow closely behind," said John Lubniewski, Chief Executive Officer and Director at HTG.

Partnering discussions have been initiated with global biopharmaceutical companies around the Company’s portfolio of drug candidate molecules in oncology and neurodegenerative disease indications. In addition, HTG has initiated partnering conversations regarding the use of HTG’s drug discovery engine within the partners’ portfolios of drug assets.

"While our partnering discussions are in early stages, we are pleased with the level of preliminary interest we have seen in our drug discovery platform from pharmaceutical companies that historically in-license candidates for preclinical development as part of their business model as well as those interested in using our AI-driven drug discovery engine with their own target portfolios," Mr. Lubniewski continued. "We believe this interest is driven by our highly differentiated approach to drug discovery, which uses our proprietary transcriptomic profiling technologies, integrated with a machine learning-based chemical library design platform, to better-inform the design and selection of drug candidate molecules. We believe that this approach will yield drug candidates with lower risk profiles and increased opportunities for development success, providing faster and more cost-efficient outcomes than traditional approaches, and believe that these potential partners are beginning to quickly understand these advantages."

First Quarter 2023 Financial Results:

Product and product-related services revenue for the quarter ended March 31, 2023 was $1.0 million, compared to $1.2 million for the same period in 2022. This revenue continues to primarily reflect sales of the Company’s two whole transcriptome products, the HTG Transcriptome and HTG EdgeSeq miRNA panels, to new and existing customers as consumables and sample processing services. Sales of these products represented 66% of revenue for the quarter ended March 31, 2023.

Net loss from operations for the quarter ended March 31, 2023 was $5.0 million, compared to $6.3 million for the same period in 2022. Net loss per share was $(2.28) for the quarter ended March 31, 2023 compared with $(9.73) for the first quarter of 2022, reflecting approximately 1.3 million additional common shares issued in December 2022. This operating margin improvement also reflects cost reduction measures implemented in the second quarter of 2022 which aligned the Company’s profiling cost structure with expected future revenue to reduce operating cash burn.

Cash, cash equivalents and investments in available-for-sale securities totaled $6.6 million as of March 31, 2023, with current liabilities of approximately $6.6 million and non-current liabilities of $3.8 million.

On May 10, 2023 Hepion Pharmaceuticals, Inc. (NASDAQ:HEPA), a clinical stage biopharmaceutical company focused on Artificial Intelligence ("AI")-driven therapeutic drug development for the treatment of fibrotic diseases, including non-alcoholic steatohepatitis ("NASH"), hepatocellular carcinoma ("HCC"), and other chronic diseases, reported that it will effect a reverse stock split of its outstanding shares of common stock at a ratio of 1-for-20, effective as of 4:01 p.m. Eastern Time today, May 10, 2023 (Press release, Hepion Pharmaceuticals, MAY 10, 2023, View Source [SID1234631376]). Hepion common stock will begin trading on a split-adjusted basis when the market opens on May 11, 2023 under the existing trading symbol "HEPA."

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As a result of the reverse stock split, the CUSIP number for the Company’s common stock will now be 426897302. The reverse stock split was previously approved by Hepion stockholders at the Special Meeting of Stockholders held on December 15, 2022, with the final ratio determined by the Company’s Board of Directors.

Upon effectiveness of the reverse stock split, every 20 shares of Hepion common stock issued and outstanding as of the effective date will be automatically combined into one share of common stock. Outstanding equity-based awards and other outstanding equity rights will be proportionately adjusted. No fractional shares will be issued as a result of the reverse stock split. Immediately after the reverse stock split becomes effective, the Company will have approximately 3,811,482 shares of common stock issued and outstanding. Stockholders of record otherwise entitled to receive a fractional share as a result of the reverse stock split will automatically be entitled to receive an additional fraction of a share of common stock to round up to the next whole share.

The reverse stock split is primarily intended to bring the Company into compliance with Nasdaq’s minimum bid price requirement.

"The shareholder-approved reverse split comes at an opportune time as we expect to soon be in a position to deliver rencofilstat’s hepatic function and NASH biomarker results from the Phase 2 ALTITUDE-NASH clinical trial. In addition, it may make our stock more attractive to institutional investors and other members of the investing public, thereby providing for a stronger and more diverse investor base," commented Robert Foster, Chief Executive Officer of Hepion.

Additional information concerning the reverse stock split can be found in Hepion’s definitive proxy statement filed with the Securities and Exchange Commission on November 21, 2022.

On May 10, 2023 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported preliminary results from 30 patients enrolled in its ongoing Phase 2, single arm study of trilaciclib administered prior to the antibody-drug conjugate (ADC), sacituzumab govitecan-hziy in patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) (Press release, G1 Therapeutics, MAY 10, 2023, View Source [SID1234631375]). These data highlight the potential for trilaciclib to meaningfully reduce adverse events related to use of sacituzumab. As expected, patients with PD-L1(+) tumors appear to respond earlier than patients with PD-L1(-) tumors. The Company expects to reach the overall survival (OS) endpoints in the first quarter of 2024.

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Data generated across multiple preclinical and clinical studies to date show that trilaciclib has the greatest effect on longer term endpoints including OS rather than earlier efficacy measures such as ORR and progression free survival (PFS), consistent with other immunotherapies like checkpoint inhibitors. These results suggest that this is likely due to trilaciclib’s immune-mediated mechanism of action that protects the immune system from the initial damage caused by ADC therapy and enhances long term immune surveillance by increasing the generation of certain memory T cells. This dual benefit may provide important longer-term benefits for patients by improving their ability to generate robust immune responses, particularly when treated with future subsequent therapies.

"These preliminary results continue to show the consistent benefit of trilaciclib when administered prior to sacituzumab, relative to the previously published single agent safety profile of this ADC, including greater than 50 percent reductions in the incidence of events including neutropenia, anemia, and diarrhea," said Raj Malik, M.D., Chief Medical Officer at G1 Therapeutics. "It is too early to determine the efficacy of trilaciclib prior to sacituzumab in this patient population. However, early indications suggest a higher response rate in patients with PD-L1 positive tumors, which commonly have an immune inflamed tumor microenvironment and are thus more likely to respond early to immunotherapies. Given that this trial includes a heavily pretreated patient population, we are enthusiastic about these data to date. We will continue to monitor efficacy to assess the potential of trilaciclib to improve overall survival – by protecting the immune system and stimulating long term immune surveillance – when combined with additional treatment regimens beyond gemcitabine/carboplatin for patients with TNBC. We look forward to these overall survival data in the first quarter of 2024."

These results are being presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Breast Cancer 2023 Annual Congress. The poster, titled, "Trilaciclib Combined with Sacituzumab Govitecan (SG) In Metastatic Triple-Negative Breast Cancer (mTNBC): Preliminary Phase 2 Results," can be found here.

Patient Demographics

As of the data cut date of April 3, 2023, all patients (N = 30) had received at least one dose of any study drug and 93.3% of patients had metastatic disease. Patients received a median (range) of 5.5 (1-20) cycles of treatment, and median follow-up was 5.5 months. Eleven (11) patients remain on study treatment and 22 patients remain in the study. In addition, a majority (73.3%; 22/30) of enrolled patients had received prior PD-(L)1 immunotherapy and 63.3% of patients had PD-L1(+) tumors.

Safety Data (n=30)

Trilaciclib was well tolerated when administered prior to sacituzumab. Safety results showed a clinically meaningful on-target effect of trilaciclib to reduce (>50%) the rates of multiple adverse events compared to the previously published sacituzumab govitecan-hziy single agent safety profile from the ASCENT trial, including myelosuppression (neutropenia, anemia) and diarrhea due to the presence of CDK4/6-expressing cells in the intestinal crypt.

Summary of Treatment Related Adverse Events (TRAE) in patients receiving
trilaciclib in combination with sacituzumab govitecan-hziy Summary of TRAEs in patients receiving sacituzumab govitecan-hziy1
(Includes TEAEs with a ≥ 10% increase with sacituzumab vs. chemotherapy)
Phase 2 trial of trilaciclib in combination with sacituzumab: TRAEs (n=30) ASCENT (no trilaciclib): TRAEs (n=258)
Adverse Event Any Grade Grade 3-4 Adverse Event Any Grade Grade 3-4
Neutropenia 30% 13% Neutropenia 63% 51%
Diarrhea 27% 3% Diarrhea 59% 10%
Nausea 30% 3% Nausea 57% 3%
Alopecia 33% 0% Alopecia 46% 0%
Fatigue 47% 0% Fatigue 45% 3%
Anemia 10% 0% Anemia 34% 8%
Vomiting 17% 3% Vomiting 29% 1%
1Adapted from Bardia A, et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med 2021;384:1529-41. DOI: 10.1056/NEJMoa2028485. Table 3

Treatment-related adverse events (TRAE) of any grade related to any study drug were reported in 76.7% of patients, the most common of which were fatigue, alopecia, nausea, and diarrhea. Adverse events (AEs) leading to treatment discontinuation of study drug occurred in one patient.

Initial Efficacy Results

With a median follow-up of 5.5 months, the efficacy of trilaciclib prior to sacituzumab in this patient population is preliminary. Initial results to date show that ORR is higher in patients with PD-L1(+) mTNBC (confirmed ORR=35.3%) relative to the overall study population (confirmed ORR=25.0%). To date, one additional patient has experienced an unconfirmed response. The median Progression Free Survival (mPFS) with trilaciclib plus sacituzumab was 4.1 months. The Company expects to reach the OS endpoints in the first quarter of 2024.

This study includes a heavily pretreated patient population, with 73.3% of patients having received prior PD-(L)1 treatment and 26.7% of patients having >3 anticancer regimens. Prior data from the ASCENT trial have shown a 34.9% ORR in the overall study population, and that patients pretreated with PD-(L)1 therapy show lower initial responses to sacituzumab (28.4% in pretreated patients vs. 37.5% in untreated patients) and a lower mPFS vs the overall population (4.2 months pretreated patients vs. 5.6 months in untreated patients) (Bardia A, et al. Figures S5 and 2).

One patient in G1’s trial to date achieved a partial response (59% reduction in the sum of longest diameters; SLD) after initial progressive disease (21% increase in SLD) with continuation of therapy at the investigator’s discretion, as the patient seemed to be deriving clinical benefit with trilaciclib and sacituzumab. This patient was not included in the confirmed response calculation. This type of improvement after continued therapy post-progressive disease has been observed with immunotherapies like checkpoint inhibitors but is not usually associated with cytotoxic therapies alone, further suggesting the potential immunotherapeutic benefit of trilaciclib.

About Triple Negative Breast Cancer (TNBC)
According to the American Cancer Society, nearly 300,000 new cases of invasive breast cancer are diagnosed annually in the U.S. Triple-negative breast cancer makes up approximately 15-20% of such diagnosed breast cancers. TNBC is cancer that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. Because mTNBC cells lack key growth-signaling receptors, patients do not respond well to medications that block estrogen, progesterone, or HER2 receptors. Instead, treating mTNBC typically involves chemotherapy, radiation, and surgery. TNBC is considered to be more aggressive and have a poorer prognosis than other types of breast cancer. In general, survival rates tend to be lower with mTNBC compared to other forms of breast cancer, and mTNBC is also more likely than some other types of breast cancer to return after it has been treated, especially in the first few years after treatment. It also tends to be higher grade than other types of breast cancer.