On May 11, 2023 Heron Therapeutics, Inc. (Nasdaq: HRTX) (the "Company"), a commercial-stage biotechnology company focused on improving the lives of patients by developing and commercializing therapeutic innovations that improve medical care, reported financial results for the three months ended March 31, 2023 and highlighted recent corporate updates (Press release, Heron Therapeutics, MAY 11, 2023, View Source [SID1234631508]).

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First quarter 2023 net product sales grew 26% to $29.6 million, compared to the first quarter of 2022. The sales growth was mainly driven by our oncology care franchise, which increased 15%, compared to the same period in 2022. First quarter also reflected continued advancement of our acute care franchise, with $3.5 million in net product sales from ZYNRELEF and initial orders from the launch of APONVIE in March.

With the appointment of Craig Collard as CEO in April and the recent hiring of Jason Grillot as VP of sales and marketing of the acute care franchise, the team is conducting a thorough review of the Company’s business practices and strategies to develop a long-term plan that maximizes the potential of the Company. We have identified two areas of immediate priority for our commercial team: first, is to enhance the value of ZYNRELEF through a broader and deeper penetration of accounts; second, to address application issues through training and expanded indications. Further, we are looking at ways to reduce cash burn through improved operational efficiency. We look forward to updating investors on these fronts in the coming months.

Acute Care Franchise

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ZYNRELEF:
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Net product sales of ZYNRELEF (bupivacaine and meloxicam) extended-release solution for the three months ended March 31, 2023 was $3.5 million.
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Since launch on July 1, 2021 through March 31, 2023, 907 unique accounts purchased ZYNRELEF with 80% of those accounts reordering the product.
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The supplemental New Drug Application (sNDA) for ZYNRELEF, to support expanded use in soft tissue and orthopedic surgical procedures remains on track for the Prescription Drug User Fee Act (PDUFA) approval goal date of October 23, 2023.

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APONVIE:
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The APONVIE (aprepitant) injectable emulsion, the only intravenous (IV) substance P/neurokinin-1 (NK1) receptor antagonist (RA) indicated for the prevention of postoperative nausea and vomiting (PONV) in adults, launched commercially in the U.S. on March 6, 2023.
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Net product sales of APONVIE for the three months ended March 31, 2023 were $0.3 million.

The Centers for Medicare and Medicaid Services granted pass-through payment status for APONVIE, effective April 1, 2023, under C-code C9145.

Oncology Care Franchise

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Oncology Care Franchise Net Product Sales: For the three months ended March 31, 2023, oncology care franchise net product sales were $25.8 million, which increased 15% from $22.4 million for the same period in 2022.
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CINVANTI Net Product Sales: Net product sales of CINVANTI (aprepitant) injectable emulsion for the three months ended March 31, 2023 were $22.8 million, compared to $20.3 million for the same period in 2022.
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SUSTOL Net Product Sales: Net product sales of SUSTOL (granisetron) extended-release injection for the three months ended March 31, 2023 were $3.0 million, compared to $2.1 million for the same period in 2022.

"We continued to make steady progress in the first quarter of 2023 at Heron, highlighted by the approval and launch of our fourth commercial product, APONVIE. We are pleased with the steady growth in the oncology care franchise and remain encouraged by the market potential for ZYNRELEF and APONVIE," said Craig Collard, new Chief Executive Officer of Heron. "Looking ahead, we are focused on reducing our cash burn and advancing a streamlined organization that we believe will begin to show significant growth while also continuing to improve patient’s lives."

Financial Results

Net product sales for the three months ended March 31, 2023 were $29.6 million, compared to $23.5 million for the same period in 2022.

For the three months ended March 31, 2023, total operating expenses were $62.7 million, compared to $86.4 million for the same period in 2022, representing a decrease of $23.7 million, or a 27% reduction year-over-year. This decrease was driven by cost management efforts and a reduction in development projects, offset by higher cost of goods sold and increased litigation expenses. Cost of product sales were $16.9 million in the first quarter of 2023, compared to $11.4 million for the same period in the prior year. The product gross margin rate decreased year-over-year primarily as a result of a one time inventory write-off due to short-dated product. Sales and marketing expenses decreased by $2.3 million, primarily due to a reduction in personnel expenses and external costs to support the ongoing commercialization of ZYNRELEF. Research and development expenses decreased by $28.3 million, primarily driven by lower personnel and project-related expenses, including manufacturing projects to increase operational efficiencies. General and administrative expenses increased by $1.3 million, primarily driven by increased litigation and activist shareholder issues.

Heron’s net loss for the three months ended March 31, 2023 was $32.8 million, or $0.27 per share, compared to $63.9 million, or $0.63 per share, for the same period in 2022. Net loss for the three months ended March 31, 2023 included non-cash, stock-based compensation expense of $7.9 million, compared to $10.9 million for the same period in 2022.

As of March 31, 2023, Heron had cash, cash equivalents and short-term investments of $60.0 million, compared to $84.9 million as of December 31, 2022. Net cash used for operating activities for the three months ended March 31, 2023 was $24.9 million, compared to $43.9 million for the same period in 2022. The decrease in our net cash used for operating activities was primarily due to a decrease in net loss, the reduction in headcount implemented in June 2022 and changes in working capital.

Conference Call and Webcast

Heron will host a conference call and webcast on May 11, 2023 at 4:30 p.m. ET. The conference call can be accessed by dialing (646) 307-1963 for domestic callers and (800) 715-9871 for international callers. Please provide the operator with the passcode 1933547 to join the conference call. The conference call will also be available via webcast under the Investor Relations section of Heron’s website at www.herontx.com. An archive of the teleconference and webcast will also be made available on Heron’s website for 60 days following the call.

About ZYNRELEF for Postoperative Pain

ZYNRELEF is the first and only dual-acting local anesthetic that delivers a fixed-dose combination of the local anesthetic bupivacaine and a low dose of nonsteroidal anti-inflammatory drug meloxicam. ZYNRELEF is the first and only extended-release local anesthetic to demonstrate in Phase 3 studies significantly reduced pain and significantly increased proportion of patients requiring no opioids through the first 72 hours following surgery compared to bupivacaine solution, the current standard-of-care local anesthetic for postoperative pain control. ZYNRELEF was initially approved by the FDA in May 2021 for use in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after bunionectomy, open inguinal herniorrhaphy and total knee arthroplasty. In December 2021, the FDA approved an expansion of ZYNRELEF’s indication. In December 2022, we submitted an sNDA to support the proposed indication for greatly expanded use of ZYNRELEF in soft tissue and orthopedic surgical procedures, and the FDA assigned a PDUFA goal date of October 23, 2023. ZYNRELEF is now indicated in the U.S. in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after foot and ankle, small-to-medium open abdominal, and lower extremity total joint arthroplasty surgical procedures. Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large multilevel spinal, and head and neck procedures.

Please see full prescribing information, including Boxed Warning, at www.ZYNRELEF.com.

About APONVIE for PONV

APONVIE is a substance NK1 RA, indicated for the prevention of PONV in adults. Delivered via a 30-second IV push, APONVIE 32 mg was demonstrated to be bioequivalent to oral aprepitant 40 mg with rapid achievement of therapeutic drug levels. APONVIE is the same formulation as Heron’s approved drug product CINVANTI. APONVIE is supplied in a single-dose vial that delivers the full 32 mg dose for PONV. APONVIE was approved by the FDA in September 2022.

Please see full prescribing information at www.APONVIE.com.

About CINVANTI for Chemotherapy Induced Nausea and Vomiting (CINV) Prevention

CINVANTI, in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin as a single-dose regimen, delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) as a single-dose regimen, and nausea and vomiting associated with initial and repeat courses of MEC as a 3-day regimen. CINVANTI is an IV formulation of aprepitant, an NK1 RA. CINVANTI is the first IV formulation to directly deliver aprepitant, the active ingredient in EMEND capsules. Aprepitant (including its prodrug, fosaprepitant) is the only single-agent NK1 RA to significantly reduce nausea and vomiting in both the acute phase (0–24 hours after chemotherapy) and the delayed phase (24–120 hours after chemotherapy). The FDA-approved dosing administration included in the U.S. prescribing information for CINVANTI include 100 mg or 130 mg administered as a 30-minute IV infusion or a 2-minute IV injection.

Please see full prescribing information at www.CINVANTI.com.

About SUSTOL for CINV Prevention

SUSTOL is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. SUSTOL is an extended-release, injectable 5-hydroxytryptamine type 3 RA that utilizes Heron’s Biochronomer drug delivery technology to maintain therapeutic levels of granisetron for ≥5 days. The SUSTOL global Phase 3 development program was comprised of two, large, guideline-based clinical studies that evaluated SUSTOL’s efficacy and safety in more than 2,000 patients with cancer. SUSTOL’s efficacy in preventing nausea and vomiting was evaluated in both the acute phase (0–24 hours after chemotherapy) and delayed phase (24–120 hours after chemotherapy).

Please see full prescribing information at www.SUSTOL.com.

On May 11, 2023 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company working to develop the world’s most potent vaccines, reported financial results for the first quarter ended March 31, 2023 and provided recent corporate and clinical updates (Press release, Gritstone Bio, MAY 11, 2023, View Source [SID1234631507]).

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"Strategically prioritizing GRANITE underscores our conviction in the program and focuses our near-term resources on the immense opportunity that lies directly ahead of us: potentially being the first to demonstrate efficacy of a neoantigen-based personalized cancer vaccine in a randomized, controlled trial for MSS-CRC," said Andrew Allen, M.D., Ph.D., Co-founder, President, and Chief Executive Officer of Gritstone bio. "GRANITE is a potentially transformative therapy that has already shown significant promise in our published Phase 1/2 study in patients with metastatic MSS-CRC, who had received two prior lines of chemotherapy. The high demand seen to date for our ongoing Phase 2 is a testament to its potential. Expanding the study from 80 to 100 patients not only increases the statistical power of the study but also generates more time-to-event data to help inform the Phase 3. We are thrilled to have the momentum and capital to expand this study and take this important step forward for patients with newly diagnosed metastatic CRC, as well as those being treated for CRC in the adjuvant setting and other cold tumors. We look forward to sharing preliminary Phase 2 efficacy data from approximately half of the 100 total patients in the first quarter of 2024."

Dr. Allen continued, "Along with the significant progress in GRANITE, the data flowing from our CORAL program is highly encouraging and provides early signals of the potential advantages of self-amplifying mRNA (samRNA) over first-generation mRNA against infectious disease. We recently observed durable neutralizing antibody titers at 6 months following samRNA vaccination in over 100 vaccine-naïve subjects treated within our CORAL-CEPI trial, where interim results were presented at ECCMID 2023. Self-amplifying mRNA has several distinct characteristics including prolonged and elevated antigen expression that suggest it could play a key role in the induction of long-term, variant-proof immune protection. We look forward to continuing to work with our collaborators to demonstrate the full potential of our samRNA platform against SARS-CoV-2 and other important viruses."

Corporate Updates

GRANITE (individualized neoantigen vaccine against cold tumors): Gritstone is focusing its resources to expand the ongoing Phase 2 portion of the Phase 2/3 study, which is evaluating GRANITE as a maintenance therapy in first-line metastatic microsatellite-stable colorectal cancer (MSS-CRC). As of May 10, 2023, the company had randomized 71 of the initially planned 80 total patients. The company plans to expand the study to randomize 100 patients in total. Enrollment of all 100 patients is expected to complete in third quarter of 2023 and preliminary data on approximately 50 of the 100 patients from the Phase 2 portion of the study (circulating tumor DNA [ctDNA] and progression-free survival data [evaluated by both RECIST and iRECIST criteria] on patients completing at least 4 months of treatment) is expected in the first quarter of 2024.

SLATE ("off-the-shelf" neoantigen vaccine program): Given the strategic decision to focus on GRANITE, the company is deferring the initiation of a randomized Phase 2 clinical trial with SLATE until 2024. Previously, a KRAS-dedicated version of SLATE demonstrated strong T cell responses and an observed survival advantage among molecular responders in Phase 1/2 studies of patients with MSS-CRC and non-small cell lung cancer (NSCLC, press release announcing ESMO (Free ESMO Whitepaper) 2022 data available here). The company believes success in GRANITE has the potential to further validate the company’s neoantigen-based approach, which SLATE and GRANITE share, and that SLATE is ready for application across solid tumor indications and shared tumor neoantigen classes.

Infectious Disease: The company will continue its ongoing clinical and preclinical infectious disease efforts as planned, with the vast majority of these efforts being funded via external collaborators. The Bill & Melinda Gates Foundation, the Coalition for Epidemic Preparedness Innovations (CEPI) and the National Institute of Allergy and Infectious Diseases (NIAID) support the company’s CORAL program. Gilead Sciences, Inc. (Gilead) is conducting a Phase 1 study as part of a collaboration with Gritstone to research and develop a therapeutic vaccine against HIV.

Clinical Program Updates
Tumor-Specific Neoantigen Oncology Programs (GRANITE and SLATE)

In April 2023, Gritstone delivered multiple presentations detailing advances in neoantigen prediction capabilities and cancer vaccine programs at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR 2023).
GRANITE (individualized neoantigen program) presentation: Longitudinal analysis of participants in the GRANITE Phase 1/2 supports vaccine-elicited priming and boosting of antigen-specific T cell populations associated with conversion of "cold" to "hot" tumors and molecular responses.
EDGE (Epitope Discovery for Genomes Platform) poster: Advances in EDGE models (Gritstone’s AI-driven neoantigen prediction platform) enable potential best-in-class prediction of class II HLA-presented neoantigens that could drive CD4+ T cell responses.
SLATE ("off-the-shelf" neoantigen vaccine program) poster: Description of a novel KRAS G12C class II epitope with evidence of clinical benefit associated with vaccine-elicited T cell response.
In February 2023, Gritstone announced it had entered into a clinical trial agreement with the National Cancer Institute to evaluate an autologous T cell therapy expressing a T cell receptor targeting mutated KRAS in combination with Gritstone’s KRAS-directed vaccine candidate, SLATE-KRAS, in a Phase 1 study led by Steven A. Rosenberg, M.D., Ph.D.
Infectious Disease Programs
CORAL – Second-generation SARS-CoV-2 vaccine program that serves as proof-of-concept for Gritstone’s infectious disease approach and the potential application of samRNA in infectious diseases.

In all studies to date, results have shown Gritstone’s samRNA vaccine candidates to be well-tolerated and capable of driving strong, durable and broad immunogenicity across several subject populations and settings.
In April 2023, Gritstone presented new data from two ongoing Phase 1 studies demonstrating persistence of high neutralizing antibodies for at least 6 months following samRNA vaccine across multiple settings and subject populations. Both datasets were presented at the 33rd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2023).

CORAL-CEPI poster: Results from Part A of the CORAL-CEPI study (total study n = 342), primary series samRNA vaccination showed to elicit strong neutralizing antibody (nAb) responses that persist for at least 6 months, including variant cross-reactive nAb, in previously unvaccinated ("vaccine-naïve") South African subjects. Enrollment in CORAL-CEPI completed in February 2023.

CORAL-BOOST poster: Results from cohorts 3 and 4 of the CORAL-BOOST study show the samRNA elicited robust nAbs, and that these nAbs persisted for at least 6 months regardless of primary series (adenovirus or mRNA). These results are generally consistent with 6-month neutralizing antibody results from cohorts 1 and 2 of the study, which evaluated samRNA as a boost following Vaxzevria (adenovirus) only (August 2022).
Enrollment in the CORAL-NIH trial completed in 2022. This study is sponsored and executed by NIAID.
HIV – Collaboration with Gilead under Gilead’s HIV Cure Program to research and develop vaccine-based HIV immunotherapy treatment.

The collaboration with Gilead to research and develop a vaccine-based HIV immunotherapy treatment remains active and ongoing.
In February 2023, results from a preclinical study conducted in collaboration with Gilead were presented at Conference on Retroviruses and Opportunistic Infections (CROI) 2023. The first data disclosed from the Gritstone-Gilead HIV Cure collaboration, results showed that simian immunodeficiency virus (SIV) Chimpanzee Adenovirus (ChAd) and self-amplifying mRNA (samRNA) vaccines induced a strong and broad CD8+ T cell immune response, which was significantly enhanced in combination with immune modulators.
First Quarter 2023 Financial Results

Cash, cash equivalents, marketable securities and restricted cash were $153.2 million as of March 31, 2023, compared to $185.2 million as of December 31, 2022.

Research and development expenses were $30.5 million for the three months ended March 31, 2023 compared to $28.2 million for the three months ended March 31, 2022. The increase of $2.3 million was primarily due to increases of $1.5 million in personnel-related expenses, $0.3 million in outside services, $0.7 million in facilities related costs, and $0.8 million in laboratory supplies, offset by a decrease of $1.0 million in milestone and license payments.
General and administrative expenses were $6.7 million for the three months ended March 31, 2023 compared to $8.0 million for the three months ended March 31, 2022. The decrease of $1.3 million was primarily attributable to decreases of $1.1 million in outside services and $0.2 million in facilities-related costs.
Collaboration, license, and grant revenues were $2.4 million for the three months ended March 31, 2023 compared to $7.2 million for the three months ended March 31, 2022. During the three months ended March 31, 2023, we recorded $0.1 million in collaboration revenue related to our collaboration with Gilead, $0.4 million in collaboration revenue related to our collaboration with 2seventy bio, Inc., $1.5 million in grant revenue from CEPI, and $0.4 million in grant revenue from the Gates Foundation. During the three months ended March 31, 2022, we recognized $4.0 million in collaboration revenue related to our collaboration with 2seventy bio, $0.7 million in collaboration revenue related to our collaboration with Gilead, $2.2 million in grant revenue from CEPI, and $0.2 million in grant revenue from the Gates Foundation.
Webcast Details
A webcast to discuss first quarter 2023 results will be held at 4:30pm ET today (May 11):
Conference call: 1-888-999-6281
Conference ID: 1754341
Webcast: View Source;tp_key=c6c637ac24

An archived replay will be accessible at View Source for 30 days following the event.

On May 11, 2023 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported that five abstracts related to imetelstat, a first-in-class telomerase inhibitor, have been accepted at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting taking place from June 8-11, 2023 in Frankfurt, Germany and virtually (Press release, Geron, MAY 11, 2023, View Source [SID1234631506]). The three EHA (Free EHA Whitepaper) abstracts on IMerge Phase 3 data expand upon and further confirm the differentiating qualities of imetelstat that can address current unmet needs for lower risk MDS patients compared to available treatments. In addition, abstracts submitted by Geron collaborators covering a translational analysis from a subset of IMerge Phase 2 patients and imetelstat MF pre-clinical data were accepted for oral and poster presentation, respectively.

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"The longer follow-up data for one-year TI and additional analyses from IMerge Phase 3 in lower risk MDS we are presenting at EHA (Free EHA Whitepaper) further confirm the unprecedented durability of imetelstat, as well as provide deeper insight into the clinically meaningful benefit/risk profile of imetelstat in these patients," said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron. "The strong correlation of reduction in MDS-associated mutations with clinical benefits observed in these patients provides strong evidence for the potential of disease modification with imetelstat. Further, patient reported outcomes presenting sustained meaningful improvement in fatigue is particularly important as fatigue is a specific concern for lower risk MDS patients, and because improvement in fatigue has not been seen with currently available treatments. Overall, as these analyses are completed and as the data continue to mature, a highly compelling and differentiated profile supporting strong clinical benefit is being reinforced for imetelstat in lower risk MDS."

IMerge Phase 3 Clinical Data – Lower Risk Myelodysplastic Syndromes (MDS)

Abstract #S165: "Continuous Transfusion Independence with Imetelstat in Heavily Transfused Non-Del(5q) Lower Risk Myelodysplastic Syndromes Relapsed/Refractory to Erythropoiesis Stimulating Agents in IMerge Phase 3"

Oral Presentation on June 9 in session s417 "MPN and MDS: Targeting red cells and platelets" (14:45-16:00 CEST)
Presenter: Uwe Platzbecker, MD, University Hospital of Leipzig

The abstract reports top-line results from IMerge Phase 3 with a data cut-off of October 2022 for the primary analysis and January 2023 for ≥1-yr transfusion independence (TI). As reported in January 2023, imetelstat demonstrated statistically significant and clinically meaningful efficacy with robust 8-week TI, 24-week TI, and 1-year TI rates.

With 3 months additional follow-up, 17.8% (21/178) of imetelstat-treated patients versus 1.7% (1/60) of placebo-treated patients achieved 1-year TI (P = 0.002), representing 63.6% of 24-week TI imetelstat responders. The continuous TI for more than one year represents substantial relief from transfusion-associated complications for this lower risk MDS patient population.

As reported in January, 39.8% (47/118) of imetelstat-treated patients versus 15.0% (9/60) of placebo-treated patients achieved the study primary endpoint of 8-week TI (P < 0.001). In addition, the rate of 8-week TI was also significantly higher for imetelstat-treated patients versus placebo-treated patients across MDS subtypes, including in RS negative and RS positive patients. Median TI duration using Kaplan Meier estimates (95% CI) was 51.6 (26.9–83.9) weeks for imetelstat-treated patients versus 13.3 (8.0–24.9) weeks for placebo-treated patients (P < 0.001). Key secondary endpoint of 24-week TI was achieved in 28.0% (33/118) of imetelstat-treated patients versus 3.3% (2/60) of placebo-treated patients (P < 0.001).

New data on variant allele frequency (VAF) reductions were also reported in the abstract. For four genes frequently mutated in MDS, the VAF reductions were greater in patients treated with imetelstat than placebo: SF3B1 (P < 0.001), TET2 (P = 0.032), DNMT3A(P = 0.019) and ASXL1 (P = NS). Furthermore, SF3B1 VAF reduction correlated with longer TI duration in imetelstat-treated patients (P < 0.001). These reductions and correlations, together with the durable and continuous TI observed in the trial, support imetelstat’s disease-modifying potential.

The most common Grade 3/4 adverse events with imetelstat were thrombocytopenia and neutropenia with similar rates of Grade ≥3 bleeding and infections observed on imetelstat and placebo. These cytopenias were of short duration, and >80% resolved to Grade ≤2 within 4 weeks. The abstract also noted no new safety signals were identified in the trial.

Abstract #S164: "Disease Modifying Activity of Imetelstat in Patients with Heavily Transfused Non-Del(5q) Lower-Risk Myelodysplastic Syndromes Relapsed/Refractory to Erythropoiesis Stimulating Agents in IMerge Phase 3"

Oral Presentation on June 11th in session "s448 MDS biology and translational updates" (11:30 – 12:45 CEST)
Presenter: Valeria Santini, MD, University of Florence School of Medicine

As noted in the abstract, a main therapeutic goal in lower risk MDS is to alter disease biology by eradicating malignant clones. MDS-initiating cells carrying cytogenetic abnormalities, mutant alleles, or both and arise from malignant stem and progenitor cells. SF3B1, involved in RNA splicing, and TET2, involved in DNA methylation, are recurrently mutated genes in lower risk MDS., Measuring change in VAF of these genes is used to denote disease burden.

Of the 178 patients enrolled in IMerge Phase 3, 22.0% of imetelstat-treated patients and 21.7% of placebo-treated patients had baseline cytogenetic abnormalities. Cytogenetic response was observed in 34.6% (9/26) of imetelstat treated patients (95% CI=17.2–55.7) versus 15.4% (2/13) of placebo-treated patients (95% CI=1.9–45.5). In addition, imetelstat-treated patients demonstrated a higher rate of ≥50% VAF decreases in SF3B1, TET2, DNMT3A, and ASXL1 mutations as compared with placebo.

Imetelstat-treated patients achieving 8-week TI, 24-week TI, and 1-year TI had higher VAF reductions in SF3B1and TET2 mutations compared with placebo-treated patients.

Additionally, both 8-week TI and 24-week TI responders on imetelstat had significantly greater VAF reductions in SF3B1 mutation versus non-responders (P<0.001, for both) on imetelstat. Importantly, greater VAF reductions in SF3B1 mutation for imetelstat-treated patients correlated significantly with hemoglobin increase; r=−0.626 (P<0.001), and longer TI duration; r=−0.549 (P<0.001). The abstract concludes that these data, taken together with robust rates of TI that are continuous and durable in the trial, may indicate improvement of the ineffective erythropoiesis characteristic of lower risk MDS with imetelstat and suggest imetelstat may alter the underlying biology of disease in these patients.

Abstract #P732: "Analysis of Patient Reported Fatigue in IMerge Phase 3 Trial of Imetelstat vs. Placebo in Heavily Transfused Non-Del(5q) Lower Risk Myelodysplastic Syndromes Relapsed/Refractory to Erythropoiesis Stimulating Agents (ESA)"

Poster on June 9 at 18:00 – 19:00 CEST
Presenter: Mikkael Sekeres, MD, University of Miami Health System and Sylvester Comprehensive Cancer Center

The abstract noted that patients with lower risk MDS and anemia experience severe fatigue that negatively impacts overall functioning and daily life. The goals for lower risk MDS treatments are to minimize transfusions and improve patient-reported outcomes (PRO). However, fatigue can also be commonly reported with currently available treatments.

In the trial, an exploratory analysis of patient-reported fatigue was conducted using Functional Assessment of Chronic Illness Therapy, or FACIT, a validated 13-item patient questionnaire, to measure the rate of deterioration or improvement of fatigue during treatment with imetelstat or placebo. Proportion of sustained meaningful deterioration/improvement was defined as percentage of patients with ≥3-point decrease/increase on the FACIT Fatigue Scale (0–52) for ≥2 consecutive treatment cycles. Time-to-deterioration/improvement was estimated by Kaplan-Meier analysis.

118 patients on imetelstat and 57 patients on placebo were assessed for PRO. Overall, 50.0% of imetelstat-treated patients reported sustained meaningful improvement in fatigue versus 40.4% of placebo-treated patients. In addition, imetelstat-treated patients reported a shorter median time to first sustained meaningful improvement in fatigue versus placebo-treated patients; 28.3 vs 65.0 weeks, respectively, hazard ratio=1.34 (95% CI, 0.82–2.20).

After 12 weeks, more imetelstat-treated patients reported improvement in the FACIT Fatigue Scale than placebo-treated patients. In addition, in imetelstat-treated patients, a significantly higher proportion of TI responders had sustained meaningful improvement in fatigue scores versus non-responders. This was consistent across 8-week TI and 24-week TI and hematologic improvement-erythroid (HI-E) response per 2006 International Working Group criteria, for imetelstat-treated patients, which was not an association observed in placebo-treated patients.

With both imetelstat- and placebo-treated patients reporting similar rates of deterioration in fatigue, these data suggest that imetelstat did not worsen the rate of deterioration, which has been reported with other available treatments. Importantly, imetelstat-treated patients were more likely to have sustained meaningful improvement in fatigue, as well as experience such improvement more quickly. The abstract concludes that a significant association between TI and HI-E responses and sustained meaningful improvement in fatigue support the clinical benefit of imetelstat treatment.

Translational Analysis from IMerge Phase 2 – Lower Risk MDS

Abstract #S169: "Modulation of the immune landscape in lower-risk myelodysplastic syndromes with imetelstat-induced transfusion independency"

Oral Presentation on June 9 in session "s417 MPN and MDS: Targeting red cells and platelets" (14:45-16:00 CEST)
Presenter: Nicolas Chapuis, Assistance Publique-Hopitaux de Paris, Centre-Universite Paris Cite

As noted in an abstract by Geron collaborators, this analysis aimed to identify biological pathways associated with the clinical response, by analyzing bone marrow mononuclear cell transcriptome and peripheral blood immune cell landscape of a subset of patients with lower risk MDS enrolled in the IMerge Phase 2 clinical trial. The abstract concludes that low inflammatory features at baseline and induction of an adaptive immune profile by imetelstat are associated with the TI response, suggesting that immune cell remodeling could contribute to hematopoietic activity of imetelstat treatment.

Imetelstat Pre-Clinical Data in Myelofibrosis (MF)

Abstract # P1008 : "The telomerase inhibitor imetelstat differentially targets JAK2V617F- versus CALR-mutant Myeloproliferative Neoplasm cells and inhibits JAK-STAT signaling"

Poster on Friday, June 9 at 18:00-19:00 CEST
Presenter: Nicolas Chatain, PhD, University Hospital Aachen

An abstract by Geron collaborators reports on a single patient study which analyzed clonal evolution of the myeloproliferative neoplasms mutation profile during a two-year course of imetelstat treatment. In the study, using the human TF-1MPL and murine 32DMPL cell lines, the authors demonstrated a stronger effect of imetelstat on CALRdel52-positive vs. JAK2V617F-positive cell viability (p=0.0361 and p=0.0311 for 5 μM imetelstat, respectively), and this was associated with an immediate downregulation of JAK2 protein phosphorylation and downstream signaling as well as a reduction of telomerase reverse transcriptase (hTERT) and STAT3 mRNA expression. The authors report these data confirm that imetelstat reduces hTERT expression and telomere length (TL) and JAK2 and CALR clones by targeting the JAK/STAT signaling, particularly in CALR-mutated cells. According to the abstract conclusion, the data propose that CALR-mutated clones are highly vulnerable to imetelstat treatment.

About IMerge Phase 3

The Phase 3 portion of the IMerge Phase 2/3 study is a double-blind, 2:1 randomized, placebo-controlled clinical trial to evaluate imetelstat in patients with IPSS Low or Intermediate-1 risk (lower risk) transfusion dependent MDS who were relapsed after, refractory to, or ineligible for, erythropoiesis stimulating agent (ESA) treatment, had not received prior treatment with either a HMA or lenalidomide and were non-del(5q). To be eligible for IMerge Phase 3, patients were required to be transfusion dependent, defined as requiring at least four units of packed red blood cells (RBCs), over an eight-week period during the 16 weeks prior to entry into the trial. The primary efficacy endpoint of IMerge Phase 3 is the rate of RBC-TI lasting at least eight weeks, defined as the proportion of patients without any RBC transfusion for at least eight consecutive weeks since entry to the trial (8-week TI). Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks (24-week TI), the duration of TI and the rate of hematologic improvement erythroid (HI-E), which is defined as a rise in hemoglobin of at least 1.5 g/dL above the pretreatment level for at least eight weeks or a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden. A total of 178 patients were enrolled in IMerge Phase 3 across North America, Europe, Middle East and Asia.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from non-clinical studies and clinical trials of imetelstat provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the U.S. Food and Drug Administration for both the treatment of adult patients with transfusion dependent anemia due to Low or Intermediate-1 risk MDS that is not associated with del(5q) who are refractory or resistant to an erythropoiesis stimulating agent, and for adult patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment. Geron plans to submit a New Drug Application (NDA) in the U.S. in June 2023 and a Marketing Authorization Application (MAA) in the EU in the second half of 2023 in the lower risk MDS indication.

On May 11, 2023 GENFIT (Nasdaq and Euronext: GNFT), a late-stage biopharmaceutical company dedicated to improving the lives of patients with rare and severe liver diseases, reported its cash position as of March 31, 2023 and revenues for the first three months of 2023 (Press release, Genfit, MAY 11, 2023, https://ir.genfit.com/news-releases/news-release-details/genfit-reports-first-quarter-2023-financial-information [SID1234631505]).

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Cash Position

As of March 31, 2023, the Company’s cash, cash equivalents and current financial assets amounted to €128.6 million compared with €222.2 million as of March 31, 2022, and €140.2 million as of December 31, 2022.

The decrease in cash, cash equivalents and current financial assets between December 31, 2022 and March 31, 2023 consists of costs arising out of the ordinary course of business related to the progress of our research and development pipeline.

The decrease in cash, cash equivalents and current financial assets between March 31, 2022 and March 31, 2023 notably includes the initial consideration of CHF40.0 million (€41.9 million) for the acquisition of Versantis AG on September 29, 2022, a payment of CHF2.4 million (€2.4 million) representing a net cash adjustment made at year end in accordance with the Versantis AG Share Purchase Agreement, and related acquisition costs totaling €1.7 million.

We expect that our existing cash, cash equivalents and current financial assets will enable us to fund our operating expenses and capital expenditure requirements until approximately the fourth quarter of 2024. This is based on current assumptions and without taking exceptional events into account, including potential milestone payments should the ELATIVE study be successful. In addition, as we continue to advance our current product candidates, conduct preclinical studies and conduct clinical trials, we expect that our cash used in operational activities will amount to approximately €60 million in 2023.

Revenues

Revenues2 for the first three months of 2023 amounted to €5.0 million compared to €3.9 million for the same period in 2022.

Of the €5.0 million in revenues for the first three months of 2023, €4.1 million is attributable to the partial recognition of the €40.0 million deferred income described below. €0.8 million is attributable to re-billings made in accordance with the 2021 licensing and collaboration agreement with IPSEN, referenced below. €0.1 million in revenue was generated from the services rendered by GENFIT to Ipsen in accordance with the Transition Services Agreement signed in 2022, in order to facilitate the transition of certain activities related to the Phase 3 clinical trial evaluating elafibranor in Primary Biliary Cholangitis.

Revenues for the first three months of 2022 are mainly attributable to the partial recognition of the €40.0 million deferred income described below.

In 2021, GENFIT received a €120.0 million upfront payment from Ipsen, out of which €80.0 million was recognized as 2021 revenue, and €40.0 million was recognized as deferred revenue. The remainder is recognized as revenue over time and in line with the progress of the ELATIVE double-blind study, in accordance with IFRS 15 and the terms of the strategic licensing and collaboration agreement with Ipsen on December 17, 2021.

On May 11, 2023 Galera Therapeutics, Inc. (Nasdaq: GRTX), a clinical-stage biopharmaceutical company focused on developing and commercializing a pipeline of novel, proprietary therapeutics that have the potential to transform radiotherapy in cancer, reported financial results for the first quarter ended March 31, 2023, and provided recent corporate updates (Press release, Galera Therapeutics, MAY 11, 2023, View Source [SID1234631504]).

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"Galera has made tremendous progress since the start of the year, securing Priority Review designation for our avasopasem NDA, raising $30 million in a registered direct offering, and expanding our commercial leadership team," said Mel Sorensen, M.D., Galera’s President and CEO. "In February, the FDA granted priority review and assigned a PDUFA date of August 9, 2023, to the NDA for avasopasem for the reduction of radiotherapy-induced severe oral mucositis in patients with head and neck cancer. In preparation for the potential U.S. commercial launch of avasopasem in 2023, we built out our commercial leadership team, appointing leading life sciences executives with demonstrated success launching and commercializing market-leading oncology therapies. We look forward to bringing avasopasem to market as potentially the first FDA approved drug for radiotherapy-induced SOM in patients with head and neck cancer."

Recent Corporate Updates

Radiotherapy-Induced Toxicity Programs:

Severe Oral Mucositis (SOM)

In February 2023, the Company announced that the U.S. Food and Drug Administration (FDA) accepted for filing and granted priority review to the New Drug Application (NDA) for avasopasem manganese (avasopasem) for radiotherapy-induced SOM in patients with head and neck cancer (HNC) undergoing standard-of-care treatment. With Priority Review designation, the Prescription Drug User Fee Act (PDUFA) target date assigned by the FDA for the NDA is August 9, 2023. The FDA indicated in its acceptance of filing letter that it is not planning to hold an advisory committee meeting on the application.
Dr. Carryn Anderson, M.D., Clinical Associate Professor of Radiation Oncology at the University of Iowa, presented a net treatment benefit analysis from the Phase 3 ROMAN trial at the European Congress on Head and Neck Oncology (ECHNO), which took place March 8-11, 2023, in Lisbon, Portugal. The analysis demonstrated the overall impact of avasopasem in reducing the burden of SOM.
Elizabeth Cullen, MSN, ARNP, Nurse Practitioner at the University of Iowa Hospitals and Clinics, presented data from the Phase 3 ROMAN trial and additional information describing the general workflow management for the infusion of avasopasem prior to radiation therapy during the Phase 3 ROMAN study at the Oncology Nursing Society (ONS) Congress, which took place April 26-30, 2023, in San Antonio, TX.
An abstract featuring avasopasem, "One-year reductions in cisplatin-related chronic kidney disease (CKD) in patients with head and neck (HNC) cancer treated with avasopasem manganese: A prespecified analysis from the phase 3 ROMAN trial," has been selected for a poster presentation as part of the Head and Neck Cancer session at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 2-6, 2023, in Chicago, IL.
Esophagitis

In May 2022, the Company announced topline results from the open-label, single-arm Phase 2a AESOP trial evaluating avasopasem for its potential to reduce the incidence of radiotherapy-induced esophagitis in patients with lung cancer. The results demonstrated that avasopasem was generally well tolerated and substantially reduced the incidence of severe esophagitis in patients with lung cancer receiving chemoradiotherapy compared to expectations based on review of historical data in the literature. Based on these data, Galera intends to pursue a strategy for avasopasem, if approved for the reduction of SOM, to support the use of avasopasem to reduce radiotherapy-induced esophagitis in patients with lung cancer as a medically accepted indication in published drug compendia.
Anti-Cancer Programs:

Locally Advanced Pancreatic Cancer (LAPC)

Enrollment is ongoing in the randomized, placebo-controlled Phase 2b GRECO-2 trial of rucosopasem in combination with stereotactic body radiation therapy (SBRT) in patients with LAPC. The primary endpoint of the trial is overall survival. The trial is enrolling well. As a result, the Company plans to expand the target enrollment from 160 to 220 patients in order to accrue the necessary events (number of deaths) for data analysis sooner. Completion of enrollment is now anticipated in the first half of 2024, and topline data readout is expected by the end of 2024.
Non-Small Cell Lung Cancer (NSCLC)

Enrollment is ongoing in the randomized, placebo-controlled Phase 2 stage of the GRECO-1 trial of rucosopasem in combination with SBRT in patients with NSCLC. Completion of enrollment continues to be anticipated in the second half of 2023, and topline data readout is expected in the second half of 2024.
General Corporate Updates

On February 17, 2023, the Company completed a registered direct offering, which resulted in the issuance and sale of 14,320,000 shares of common stock and warrants to purchase up to 14,320,000 shares of common stock at a combined offering price of $2.095 per share and accompanying warrant, generating gross proceeds of $30 million. The Company received net proceeds of $27.6 million, after deducting placement agent fees and offering expenses.
On May 1, 2023, the Company expanded its commercial leadership team with the appointment of accomplished pharmaceutical sales, market access, and commercial operations executives, including Patrick Campbell as Vice President of Sales & Account Management, Elizabeth Turner as Vice President of Market Access, and Henning Thorsen as Vice President of Commercial Operations. The new executives joined Lorraine Walker, Pharm.D., the Company’s Vice President of Marketing. Under the direction of the Company’s Chief Commercial Officer, Mark Bachleda, Pharm.D., MBA, the team is responsible for building out commercial operations, strategy development, and execution in preparation for the potential U.S. commercial launch of avasopasem in 2023.
First Quarter 2023 Financial Highlights

Research and development expenses were $7.3 million in the first quarter of 2023, compared to $8.1 million for the same period in 2022. The decrease was primarily attributable to a decrease in avasopasem development costs, partially offset by an increase in rucosopasem development costs.
General and administrative expenses were $6.6 million in the first quarter of 2023, compared to $5.0 million for the same period in 2022. The increase was primarily attributable to avasopasem commercial preparations.
Galera reported a net loss of $(17.7) million, or $(0.50) per share, for the first quarter of 2023, compared to a net loss of $(15.4) million, or $(0.58) per share, for the same period in 2022.
As of March 31, 2023, Galera had cash, cash equivalents and short-term investments of $47.8 million. Galera expects that its existing cash, cash equivalents and short-term investments will enable Galera to fund its operating expenses and capital expenditure requirements into the fourth quarter of 2023.