On August 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 diseases, reported its financial results for the second quarter ended June 30, 2023, and provided a business update (Press release, Immunocore, AUG 10, 2023, View Source [SID1234634194]).

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"I am extremely pleased that KIMMTRAK is reaching more patients, with approvals now in over 35 countries, leading to another excellent quarter," said Bahija Jallal, Chief Executive Officer of Immunocore. "I am also excited by the progress of our pipeline, as we announce the first Phase 3 trial with our PRAME-targeted ImmTAC, in first-line cutaneous melanoma."

"IMC-F106C, the first PRAME-targeted bispecific therapy, has demonstrated durable clinical activity in melanoma as monotherapy, leading us to initiate the PRISM-MEL301 Phase 3 trial," commented David Berman, EVP Research and Development, Immunocore. "This melanoma trial, informed by a Type B FDA meeting and with global expert input, will randomize patients to IMC-F106C with nivolumab versus global standards of care of nivolumab with or without relatlimab."

Second Quarter 2023 Highlights (including post-period)

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

KIMMTRAK is approved in over 35 countries globally. Total net product revenue (or "net sales") arising from the sale of KIMMTRAK was £45.5 million (or $57.8 million) in the second quarter of 2023, of which £32.8 million (or $41.7 million) was in the United States, £12.2 million (or $15.5 million) in Europe, and £0.5 million (or $0.6 million) in the rest of the world.

In the United States, growth was driven both by patient expansion and duration of therapy. The Company estimates market share increased to approximately 60% of first-line HLA-A*02:01 positive patients with mUM and that duration of therapy in the real-world setting is tracking towards the greater than nine months seen in the Phase 2 and Phase 3 clinical trials.

In the first half of the year, the Company launched KIMMTRAK in Austria and Israel and, most recently, in Italy and Finland. In France and Germany, KIMMTRAK remains the standard of care for first-line HLA-A*02:01 positive patients with mUM, with nearly all patients in Germany being treated in first-line. In early August, the Company reached a KIMMTRAK pricing reimbursement agreement in Germany. This price, expected to be published in September 2023, is slightly improved from the Company’s accounting assumptions. The Company expects to launch KIMMTRAK in several additional European countries by the end of 2023.

In July, the Centers for Medicare & Medicaid Services (CMS) released the 2024 Proposed Rule for the physician fee schedule. The Proposed Rule names KIMMTRAK as a medicine identified as meeting the proposed criteria for unique circumstances, whereby it would have a proposed increased applicable percentage of unused or discarded product volume subject to refund to CMS, of 45%, and not 10% used for medicines without these unique circumstances. The Proposed Rule is expected to be finalized during the fourth quarter of 2023 with an effective date of January 1, 2024.

In the second quarter, the Company presented data demonstrating:

association between early circulating tumor DNA (ctDNA) reduction and longer overall survival (OS) at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting and American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2023 meeting. ctDNA clearance was higher in previously untreated mUM (37%) compared to previously treated mUM (13%). These data suggest that early ctDNA reduction may be a better predictor of longer OS than radiographic response.
final analysis, minimum follow-up of 3 years, from the Phase 2 trial in mUM at AACR (Free AACR Whitepaper) 2023. The Company plans to present updated 3-year overall survival data from the Phase 3 trial in mUM at a medical conference later this year.
In the second quarter, Sanofi informed Immunocore that they will not be progressing their evaluation of SAR444245 in combination with KIMMTRAK. As such, Sanofi elected to terminate the previously announced clinical trial collaboration, in which Sanofi was responsible for clinical development. Immunocore is no longer responsible for supplying KIMMTRAK for this clinical trial and no other costs are expected.

TEBE-AM – Phase 2 / 3 trial with KIMMTRAK in second-line or later cutaneous melanoma

Randomization continues in the Phase 2/3 clinical trial of KIMMTRAK in HLA-A*02:01 positive patients with second-line or later cutaneous melanoma. The trial is randomizing patients with advanced melanoma who have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a BRAF inhibitor. Patients are being randomized to one of three arms, including KIMMTRAK as monotherapy or in combination with an anti-PD1, and a control arm. The Company presented a trial-in-progress poster at the ASCO (Free ASCO Whitepaper) 2023 meeting, describing the design of the trial, which has a dual primary endpoint of OS and ctDNA reduction. The company expects to complete randomization of the Phase 2 portion of the study in the second half of 2024.

PRISM-MEL301 – First PRAME Phase 3 trial with IMC-F106C in first-line cutaneous melanoma

The Company, following U.S. Food and Drug Administration (FDA) Type B interaction, is planning a registrational Phase 3 trial with IMC-F106C, with the goal of starting by the first quarter of 2024. The trial will randomize patients with HLA-A*02:01 positive, first-line cutaneous melanoma to IMC-F106C + nivolumab versus a control arm of either nivolumab or nivolumab + relatlimab, depending on country. Based on feedback from the FDA, including Project Optimus, the study will initially randomize to three arms – two well-tolerated and clinically active F106C dose regimens (40 mcg and 160 mcg) and the control arm – and will discontinue one of the F106C dose regimens after an initial review of the first 60 patients randomized to the two experimental arms (90 patients randomized total). The Company plans to randomize the first patient in this trial in the first quarter of 2024. The Company estimates there are over 10,000 newly diagnosed HLA-A*02:01 positive, advanced cutaneous melanoma patients in the G7 per year.

Phase 1/2 IMC-F106C targeting PRAME-A02 in multiple solid tumors

In addition to progressing IMC-F106C into a registrational trial in advanced melanoma, the Company is continuing to enroll patients in the Phase 1/2 trial monotherapy and combination arms across multiple tumor types, including expansion arms for patients with advanced ovarian, non-small cell lung, endometrial, and melanoma cancers. Today, the Company is providing an updated analysis of the original 18 melanoma patients (initially presented at ESMO (Free ESMO Whitepaper) in September 2022), which continues to show promising durability of the clinical activity (range of duration of partial response from 6 months to 17 months). The Company expects to report data from the trial in the first half of 2024.

Early oncology pipeline: IMC-R117C (PIWIL1), IMC-P115C (PRAME-A02 HLE), IMC-T119C (PRAME-A24)

The Company is on-track to submit an IND / CTA in the fourth quarter of 2023 for IMC-R117C, an ImmTAC targeting the PIWIL1 protein for colorectal and other gastrointestinal cancers. The Company believes this is the first PIWIL1-targeted immunotherapy in development. The Company continues to work on expanding the PRAME franchise, with pre-clinical work ongoing for two new PRAME ImmTAC candidates, IMC-P115C (PRAME-A02 HLE) and IMC-T119C (PRAME-A24) for solid tumors, with both on-track for IND/CTA submission in 2024.

IMC-M113V and IMC-I109V: aiming for functional cure in HIV and HBV

The Company is enrolling people living with HIV in the multiple ascending dose (MAD) part of a Phase 1 trial with IMC-M113V, 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 part of the trial will enroll up to 28 participants. The Company expects to present a data update in 2024.

In the ongoing Phase 1 trial with IMC-I109V, enrolling people living with HBV in the single ascending dose portion, the Company has amended the study to include HBV-positive hepatocellular carcinoma in the multiple ascending dose portion of the study.

Financial Results

Total net product revenue arising from the sale of KIMMTRAK was £45.5 million ($57.8 million) and £87.6 million (£111.3 million) in the three and six months ended June 30, 2023, respectively, of which £32.8 million ($41.7 million) and £62.3 million ($79.2 million) was in the United States, £12.2 million ($15.5 million) and £24.5 million ($31.2 million) was in Europe, and £0.5 million ($0.6 million) and £0.7 million ($0.9 million) was in the rest of the world. For the three and six months ended June 30, 2022, the Company recorded total net product and pre-product revenue of £27.7 million and £38.2 million, respectively.

For the three and six months ended June 30, 2023, the Company’s research and development expenses were £28.8 million ($36.6 million) and £57.2 million ($72.7 million), respectively, as compared to £20.2 million and £38.7 million for the three and six months ended June 30, 2022, respectively. For the three and six months ended June 30, 2023, the selling and administrative expenses were £33.9 million ($43.1 million) and £67.2 million ($85.4 million), respectively, compared to £18.8 million and £38.9 million for the three and six months ended June 30, 2022, respectively.

Basic and diluted loss per share for the three and six months ended June 30, 2023 was £0.29 ($0.37) and £0.64 ($0.81), respectively, compared to a basic and diluted loss per share of £0.14 and £0.51 for the three and six months ended June 30, 2022, respectively.

Cash and cash equivalents were £342.3 million ($435.1 million) as of June 30, 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 June 30, 2023 into U.S. dollars at a rate of £1.00 to $1.2709.

Audio Webcast

Immunocore will host a conference call today, August 10, 2023 at 8:00 A.M. EDT/ 1:00 PM BST, to discuss the second quarter financial results and provide a business update. The call will also be available via webcast by visiting the Events & Presentations section on Immunocore’s website. A replay of this webcast will be available for 30 days.

Conference Call Details:
U.S. (toll-free): 877-405-1239
International (toll): +1 201-389-0851

Upcoming Investor Conference

H.C. Wainwright Immune Cell Engager Virtual Conference

Fireside Chat: Thursday, August 17, 2023, at 1:00 pm ET

About PRISM-MEL301 – Phase 3 trial with IMC-F106C (PRAMExCD3) in 1L advanced, cutaneous melanoma

The Phase 3 registrational trial will randomize patients with previously untreated, HLA-A*02:01 positive, advanced melanoma to IMC-F106C+nivolumab versus nivolumab or nivolumab + relatlimab, depending on country. The study will initially randomize to three arms: two F106C dose regimens (40 mcg and 160 mcg) and control arm, and will discontinue one of the F106C dose regimens after an initial review of the first 60 patients randomized to the two experimental arms (90 patients randomized total). The primary endpoint of the trial is progression free survival (PFS) by BICR, with secondary endpoints of overall survival (OS) and overall response rate (ORR).

About TEBE-AM – Phase 2 / 3 trial with tebentafusp (gp100xCD3) in second-line or later cutaneous melanoma

The trial is randomizing patients with second line or later cutaneous 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.

About ImmTAV molecules and infectious diseases

ImmTAV (Immune mobilizing monocolonal TCRs Against Virus) molecules are novel bispecific molecules that, like ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules, are designed to enable the immune system to recognize and eliminate virally infected cells.

Immunocore is advancing clinical candidates to cure patients with HIV and HBV. The Company aims to achieve a reduction in viral reservoirs to enable sustained control of HIV after stopping antiretroviral therapy (ART), without the risk of virological relapse or onward transmission. This is known as ‘functional cure’. For the treatment of HBV, the Company aims to achieve sustained loss of circulating viral antigens and markers of viral replication after stopping medication for people living with chronic hepatitis B.

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 August 10, 2023 Immatics N.V. (NASDAQ: IMTX, "Immatics"), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, reported the initiation of a Phase 1/2 clinical trial with its proprietary Bispecific T cell engaging receptor (TCER) IMA402 (Press release, Immatics, AUG 10, 2023, View Source [SID1234634193]). IMA402 is the second product candidate in Immatics’ TCER pipeline of next-generation, half-life extended bispecific molecules to enter clinical development. It targets an HLA-A*02:01-presented peptide derived from PRAME, a clinically established cancer target frequently expressed in a large variety of solid tumors.

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The Phase 1/2 clinical trial (NCT05958121) investigates TCER IMA402 in HLA-A*02:01-positive patients with PRAME-expressing recurrent and/or refractory solid tumors. The dose escalation part of the study is designed as a basket trial in focus indications to accelerate signal finding. Initial focus indications are cutaneous and uveal melanoma, ovarian cancer, lung cancer, uterine cancer and synovial sarcoma, among others.

"The addition of IMA402 to our clinical pipeline is a truly exciting step and aligns with our strategic goal to harness the full potential of PRAME, one of the most promising cancer targets in solid tumors. With our half-life extended format, we believe IMA402 has the potential to be an attractive treatment option by enhancing efficacy, minimizing toxicities, and providing favorable dosing regimen for cancer patients.," said Cedrik Britten, Chief Medical Officer at Immatics. "We are working with urgency to bring IMA402 to a broad patient population as quickly as possible and look forward to sharing first clinical data in 2024."

Primary objectives of the IMA402 Phase 1/2 trial are to determine the maximum tolerated dose (MTD) and/or the recommended doses for trial extensions, as well as to characterize safety and tolerability of IMA402. Secondary objectives are to evaluate anti-tumor activity and assess pharmacokinetics of IMA402. The Phase 1a dose escalation will be followed by a Phase 1b dose expansion, with the plan then to initiate a Phase 2 with indication-specific cohorts and/or combination therapies. Immatics has implemented an adaptive design for the dose escalation with the goal of accelerating the clinical development timeline of IMA402. Pharmacokinetics data will be assessed throughout the trial and might provide an early opportunity for adjustment of the treatment interval based on the half-life extended TCER format. The trial is initially planned to be conducted at approximately 15 sites in Europe, with extension into the US at dose expansion stage. The Phase 1a is designed to enroll approximately 45 patients.

The trial initiation is based on the comprehensive preclinical studies with IMA402 presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022.

TCER IMA402 is the second Immatics clinical program targeting PRAME, with the first being ACTengine IMA203, a TCR-T cell therapy which is currently being evaluated in a Phase 1b dose expansion. Both approaches, ACTengine and TCER, are distinct therapeutic modalities that Immatics believes to have the potential to provide innovative treatment options for a variety of cancer patient populations with different medical needs.

About IMA402
TCER IMA402 is a drug candidate owned by Immatics. IMA402 is Immatics’ second TCER molecule from the bispecifics pipeline and is directed against an HLA-A*02-presented peptide derived from preferentially expressed antigen in melanoma (PRAME), a protein frequently expressed in a large variety of solid cancers, thereby supporting the program’s potential to address a broad cancer patient population. Immatics’ PRAME peptide is present at a high copy number per tumor cell and is homogenously and specifically expressed in tumor tissue. The peptide has been identified and characterized by Immatics’ proprietary mass spectrometry-based target discovery platform, XPRESIDENT. IMA402 is part of Immatics’ strategy to leverage the full clinical potential of targeting PRAME, one of the most promising targets for TCR-based therapies.

About TCER
Immatics’ next-generation half-life extended TCER molecules are antibody-like "off-the-shelf" biologics that leverage the body’s immune system by redirecting and activating T cells towards cancer cells expressing a specific tumor target. The design of the TCER molecules enables the activation of any T cell in the body to attack the tumor, regardless of the T cells’ intrinsic specificity. Immatics proprietary biologics are engineered with two binding regions: a TCR domain and a T cell recruiter domain. The TCER format is designed to maximize efficacy while minimizing toxicities in patients. It contains a high-affinity TCR domain that is designed to bind specifically to the cancer target peptide on the cell surface presented by an HLA molecule. The antibody-derived, low-affinity T cell recruiter domain is directed against the TCR/CD3 complex and recruits a patient’s T cells to the tumor to attack the cancer cells. With a low-affinity recruiter aiming for optimized biodistribution and enrichment of the molecule at the tumor site instead of the periphery, TCER are engineered to reduce the occurrence of immune-related adverse events, such as cytokine release syndrome. In addition, the TCER format consists of an Fc-part conferring half-life extension, stability, and manufacturability. TCER are "off-the-shelf" biologics and thus immediately available for patient treatment. They can be distributed through standard pharmaceutical supply chains and provide the opportunity to reach a large patient population without the need for specialized medical centers.

On August 10, 2023 IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported a business update and announced financial results for the second quarter ended June 30, 2023 (Press release, Ideaya Biosciences, AUG 10, 2023, View Source [SID1234634192]).

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"We are executing on our clinical strategy to deliver precision medicine therapies to patients and build value for our shareholders. Our broad clinical pipeline includes three potential first-in-class clinical candidates for which we own or control all worldwide commercial rights – darovasertib (PKC), IDE397 (MAT2A) and IDE161 (PARG). We have a fourth potential first-in-class clinical candidate, GSK101 (Pol Theta Helicase), pending clearance of the IND, which will be evaluated in combination with niraparib in a GSK-sponsored clinical trial," said Yujiro S. Hata, Chief Executive Officer, IDEAYA Biosciences.

"We are initiating clinical studies which have the potential to be broadly impactful to uveal melanoma patients throughout their journey – including a Phase 2 clinical trial for single-agent darovasertib as neoadjuvant and adjuvant therapy in primary UM and a registrational trial for

Exhibit 99.1

the darovasertib and crizotinib combination in first-line, HLA-A2(-) metastatic UM," said Dr. Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

"Additionally, a first patient has been dosed in the Amgen-sponsored Phase 1/2 clinical trial evaluating IDE397 in combination with AMG 193 in MTAP-deletion tumors, with an estimated enrollment of approximately 180 patients and an expansion focus on NSCLC. We are also advancing IDE397 in a Phase 2 monotherapy expansion in high-priority MTAP deletion tumors – NSCLC, bladder, gastric and esophageal cancers. We are encouraged by the responses observed in multiple high-priority MTAP deletion tumors. Enrollment into the dose escalation of our Phase 1/2 clinical trial for IDE161 is ongoing. Lastly, we are anticipating IND clearance for evaluation of GSK101, our Pol Theta Helicase inhibitor, in the GSK-sponsored Phase 1/2 clinical trial in combination with niraparib," continued Dr. Beaupre.

IDEAYA is advancing darovasertib, its protein kinase C, or PKC, inhibitor, with a clinical strategy to broadly address uveal melanoma, or UM, in both primary and metastatic disease settings. The company has initiated a potential registration-enabling Phase 2/3 clinical trial to evaluate the darovasertib and crizotinib combination in first-line HLA-A2(-) metastatic UM. IDEAYA also initiated a company-sponsored Phase 2 clinical trial for evaluating single-agent darovasertib as neoadjuvant and adjuvant therapy in primary UM.

IDEAYA is evaluating IDE397 as monotherapy in a Phase 2 expansion cohort in patients having tumors with methylthioadenosine phosphorylase, or MTAP, deletion, including high-priority NSCLC, bladder, gastric and esophogeal cancers. Amgen has initiated and dosed a first patient in the Amgen-sponsored Phase 1/2 clinical trial evaluating IDE397, IDEAYA’s methionine adenosyltransferase 2a, or MAT2A, inhibitor, in combination with AMG 193, the Amgen investigational MTA-cooperative PRMT5 inhibitor, in patients having tumors with MTAP gene deletion.

IDEAYA is evaluating IDE161, its poly (ADP-ribose) glycohydrolase, or PARG, inhibitor, in a Phase 1/2 clinical trial in patients having tumors with homologous recombination deficiency, or HRD. IDEAYA is enrolling patients into the Phase 1 dose escalation portion of the clinical trial. The company is planning for expansion cohorts in ER+, Her2- HRD breast cancer patients, HRD ovarian cancer patients and other HRD solid tumors.

The company is anticipating IND clearance in the third quarter of 2023 to enable the GSK-sponsored Phase 1/2 clinical trial to evaluate its Pol Theta Helicase inhibitor, GSK101 (IDE705), in combination with niraparib for patients having tumors with HR mutations such as BRCA mutations, or with homologous recombination deficiency, or HRD. Subject to IND clearance for GSK101, IDEAYA will be entitled to receive a $7 million milestone payment from GSK.

The company’s preclinical pipeline includes several potential first-in-class precision medicine therapeutics. The Werner Helicase program continues in collaboration with GSK toward a development candidate nomination in the second half of 2023. IDEAYA will be entitled to receive a $3 million milestone payment from GSK in connection with IND-enabling studies for the selected development candidate.

Program Updates

Exhibit 99.1

Key highlights for IDEAYA’s pipeline programs include:

Darovasertib – PKC Inhibitor in Tumors with GNAQ or GNA11 Mutations

Darovasertib is a potent, selective inhibitor of PKC which the company is developing for genetically defined cancers having GNAQ or GNA11 gene mutations. PKC is a protein kinase that functions downstream of the GTPases GNAQ and GNA11. IDEAYA is pursuing a clinical strategy for darovasertib to broadly address uveal melanoma, alternatively referred to as ocular melanoma, in both primary and metastatic disease.

IDEAYA owns or control all commercial rights in its darovasertib program, including in MUM and in primary UM, subject to certain economic obligations pursuant to its exclusive, worldwide license to darovasertib with Novartis.

Darovasertib / Crizotinib Combination Therapy in Metastatic Uveal Melanoma

IDEAYA initiated a potential registration-enabling Phase 2/3 clinical trial, designated as IDE196-002, with clinical sites open and recruiting patients for enrollment, to evaluate the darovasertib and crizotinib combination in first-line HLA-A2(-) MUM. Highlights:

•
In April, 2023, the company reported data from its ongoing Phase 2 clinical trial, designated as IDE196-001, demonstrating compelling clinical efficacy of the darovasertib and crizotinib combination therapy in first-line and any-line MUM patients. The reported data included a safety and clinical efficacy profile for evaluable first-line (n=20) and any-line (n=63) patients, who were treated at the expansion dose of 300 mg twice-a-day darovasertib and 200 mg twice-a-day crizotinib. The evaluable patients generally had a significant disease burden and were heavily pre-treated. The reported data were preliminary and based on investigator review from an unlocked database as of the data analyses cutoff date of March 8, 2023.
o
In 20 evaluable first-line MUM patients, the investigator-reviewed data by RECIST 1.1 included: 45% overall response rate, or ORR, 90% disease control rate, or DCR, and approximately seven months median progression free survival, or PFS.
o
In 63 evaluable any-line MUM patients, the investigator-reviewed data by RECIST 1.1 included: 30% ORR, 87% DCR, and approximately seven months median PFS.
o
In a subset of 20 evaluable hepatic-only MUM patients – first-line and pre-treated patients with only hepatic metastases, the investigator-reviewed data by RECIST 1.1 included: 35% ORR, 100% DCR and approximately 11 months median PFS.
o
Clinical efficacy was observed irrespective of HLA-A2 status, including in HLA-A2(-) and HLA-A2(+) serotypes.
o
The darovasertib and crizotinib combination therapy demonstrated a manageable adverse event profile in MUM patients (n=68) at the combination expansion doses, with a low rate of drug-related serious adverse events (SAEs), and a low rate of patients who discontinued treatment with either darovasertib or crizotinib due to a drug-related adverse event.
Exhibit 99.1

•
In May 2023, IDEAYA expanded its relationship with Pfizer under the Second Pfizer Agreement to support the Phase 2/3 registrational trial to evaluate darovasertib and crizotinib as a combination therapy in MUM, pursuant to which Pfizer will provide the company with a first defined quantity of crizotinib at no cost, as well as an additional second defined quantity of crizotinib at a lump-sum cost. IDEAYA anticipates that the supply of crizotinib under the Second Pfizer Agreement, as amended, will be sufficient to support the planned Phase 2 and Phase 3 portions of the Phase 2/3 registrational trial.
•
The company is planning for darovasertib clinical program updates in the fourth quarter of 2023, including ctDNA data from Phase 2 MUM trial at the European Society for Medical Oncology’s Congress in October 2023, or ESMO (Free ESMO Whitepaper) 2023. Other potential updates may also include a summary of the prevalence of HLA-A2(-) and HLA-A2(+) serotypes from IDEAYA’s data set of approximately 145 MUM patients enrolled in clinical trials evaluating darovasertib.
Darovasertib—Design of Registration-Enabling Clinical Trial in First-Line HLA-A2*02:01(-) MUM

The protocol of the Phase 2/3 clinical trial design incorporates guidance and feedback following a Type C meeting with the FDA in March 2023. Highlights:

•
Design: Integrated Phase 2/3 open-label study-in-study in first-line, or 1L, MUM patients with an HLA-A(-)serotype; median PFS as Phase 2 primary endpoint for potential accelerated approval; patients enrolled in Phase 2 will continue on treatment within the same study and will be considered, together with additional enrolled patients, to support overall survival, or OS as Phase 3 primary endpoint for potential approval.
•
Phase 2: ~230 patients total, of which ~200 patients will be randomized on a 2:1 basis for treatment with the darovasertib and crizotinib combination in the treatment arm or investigators choice in the control arm, selected from a combination of ipilimumab (ipi) and nivolumab (nivo), PD1-targeted monotherapy or dacarbazine, and of which ~30 will support a nested study to confirm the move forward combination dose for the integrated Phase 2/3 clinical trial; potential accelerated approval based on Phase 2 median PFS by blinded independent central review, or BICR, as a primary endpoint.
•
Phase 3: ~120 additional patients with 2:1 randomization on the same basis as Phase 2, supplementing the ~200 patients enrolled in the Phase 2 and continuing on treatment at the selected treatment dose, to support data analysis for Phase 3 efficacy; potential approval based on Phase 3 median OS by BICR as a primary endpoint.
Darovasertib—Strategy for HLA-A2*02:01 Positive MUM

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Based on preliminary analyses of darovasertib clinical data from the monotherapy and combination arms of the clinical trial, and based on the darovasertib mechanism of action, darovasertib clinical activity is independent of Human Leukocyte Antigen, or HLA, serotype in UM, MUM and other GNAQ/11-mutation cancers.
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Accordingly, IDEAYA is planning to separately address MUM patients with an HLA-A*02:01 positive serotype. The company is planning to enroll HLA-A2(+) patients into a separate clinical trial, such as its ongoing Phase 2 clinical trial evaluating the darovasertib and
Exhibit 99.1

crizotinib combination treatment. Clinical efficacy data from the HLA-A2(+) patients in this clinical trial could support publication and potential inclusion in NCCN Clinical Practice Guidelines in Oncology.
Darovasertib as Neoadjuvant / Adjuvant Therapy in Primary Uveal Melanoma

IDEAYA is clinically evaluating the potential for darovasertib as neoadjuvant and/or adjuvant therapy, or (neo)adjuvant therapy, in primary UM patients.

Preliminary clinical data in the neoadjuvant setting show evidence of anti-tumor activity and support further clinical evaluation of darovasertib to determine its potential as a neoadjuvant therapy or an adjuvant therapy. Clinical objectives as neoadjuvant therapy are to save the eye by avoiding enucleation and/or to reduce the tumor thickness in the eye, enabling treatment with less radiation to preserve vision. As an adjuvant therapy, a clinical goal is to potentially extend relapse free survival. Highlights:

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IDEAYA initiated, with clinical sites open and recruiting patients for enrollment into, a company-sponsored Phase 2 clinical trial, designated as IDE196-009, to evaluate darovasertib as neoadjuvant treatment of UM prior to primary interventional treatment of enucleation or radiation therapy, and also as adjuvant therapy following the primary treatment. The clinical protocol includes neoadjuvant treatment with darovasertib to maximum benefit up to six months, primary treatment, then up to six months of follow-up adjuvant therapy.
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Neoadjuvant – Enucleation Cohort: UM patients with large tumors will be treated with darovasertib until maximum benefit or six months, at which time they will undergo a primary interventional treatment. The neoadjuvant endpoint for this large-sized tumor cohort is eye preservation. For example, a patient who would otherwise have undergone enucleation would instead be eligible for radiation treatment.
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Neoadjuvant – Radiation (e.g., Brachytherapy) Cohort: UM patients with small or medium tumors will be treated with darovasertib until maximum benefit or six months, at which time they will undergo radiation therapy. The neoadjuvant endpoints for this small or medium-sized tumor cohort include (i) reducing the radiation dose that the patient receives, relative to the radiation dose they would have otherwise received without the neoadjuvant treatment and (ii) functional vison preservation.
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Adjuvant – In the adjuvant setting, each of the two neoadjuvant cohorts will be treated with darovasertib for up to six months as follow-up adjuvant therapy after the primary interventional treatment. The adjuvant endpoints for this portion of the clinical trial include relapse free survival and useful vision.
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In April 2023 and June 2023, the company reported clinical data demonstrating clinical activity for darovasertib as neoadjuvant therapy in primary UM, including tumor shrinkage in ocular tumor lesions. Data was reported from an ongoing IST evaluating darovasertib in (neo)adjuvant primary UM, from a compassionate use protocol in neoadjuvant UM and from patients having an ocular tumor lesion during their course of treatment in the Phase
Exhibit 99.1

1 and Phase 1/2 clinical trial evaluating darovasertib as monotherapy or in combination with crizotinib in MUM. Ocular tumor shrinkage was measured with best tumor response measurement based on maximal percent reduction in measured apical height or longest basal diameter. The reported investigator-reviewed data included:
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Tumor shrinkage of primary ocular lesions in nine of nine (100%) primary or metastatic UM patients treated as monotherapy or in combination with crizotinib
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Ocular tumor shrinkage in six of six (100%) primary UM patients treated with darovasertib (n=5) or in combination with crizotinib (n=1) as neoadjuvant therapy, including one patient with a partial response (~31% ocular tumor shrinkage) at one month of treatment, three patients with ~22-24% ocular tumor shrinkage after 1, 2 or 4 months of treatment and one patient with ~80% ocular tumor shrinkage after 4 months of treatment.
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Two reported cases – first and second initial cases – of primary UM patients who were spared enucleation and were able to retain vision. One patient, who was already blind in one eye from vascular disease and was treated under a compassionate use protocol, observed an 80% reduction in ocular tumor size following fourth months of neoadjuvant treatment with darovasertib in combination with crizotinib. A second patient, who was treated in the NADOM IST, observed a 24% reduction in ocular tumor size following four months of neoadjuvant treatment with darovasertib as monotherapy. In each of these cases, the neoadjuvant treatment enabled plaque brachytherapy as a primary interventional treatment rather than an originally planned enucleation.
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IDEAYA is additionally supporting evaluation of single-agent darovasertib as (neo)adjuvant therapy in primary UM in an ongoing IST captioned as "Neoadjuvant / Adjuvant trial of Darovasertib in Ocular Melanoma" (NADOM) and led by St. Vincent’s Hospital in Sydney with the participation of Alfred Health and the Royal Victorian Eye and Ear Hospital in Melbourne.
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IDEAYA is targeting a clinical data update in the fourth quarter of 2023 from the NADOM IST evaluating single-agent darovasertib as neoadjuvant therapy in primary UM patients.
Darovasertib Orphan Drug Designation in UM and Fast Track Designation in MUM

In April 2022, the FDA designated darovasertib as an Orphan Drug in UM, including primary and metastatic disease under 21 C.F.R Part 316. Under an Orphan Drug designation, darovasertib may be entitled to certain tax credits for qualifying clinical trial expenses, exemption from certain user fees and, subject to FDA approval of a new drug application, or NDA, for darovasertib in UM, seven years of statutory marketing exclusivity. As an FDA-designated Orphan Drug, darovasertib may also be excluded from certain mandatory price negotiation provisions of the 2022 Inflation Reduction Act.

In November 2022, the FDA granted Fast Track designation to IDEAYA’s development program investigating darovasertib in combination with crizotinib in adult patients being treated for MUM. The Fast Track designation makes IDEAYA’s darovasertib and crizotinib development

Exhibit 99.1

program eligible for various expedited regulatory review processes, including generally more frequent FDA interactions, such as meetings and written communications, potential eligibility for rolling review of a future NDA and potential accelerated approval and priority review of an NDA.

IDE397—MAT2A Inhibitor in Tumors with MTAP Deletion

IDEAYA is clinically evaluating IDE397, a potent and selective small molecule inhibitor targeting methionine adenosyltransferase 2a (MAT2A), in patients having solid tumors with methylthioadenosine phosphorylase (MTAP) deletion, a patient population estimated to represent approximately 15% of solid tumors. IDEAYA is continuing clinical development of IDE397 in its Phase 1/2 clinical trial, designated as IDE397-001 (NCT04794699).

The IDE397 clinical development strategy is focused as monotherapy in select indications and on the IDE397 combination with AMG193, the Amgen investigational MTA-cooperative PRMT5 inhibitor.

IDEAYA owns all right, title and interest in and to IDE397 and the MAT2A program, including all worldwide commercial rights thereto. Highlights:

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First patient dosed in Amgen-sponsored Phase 1/2 clinical trial evaluating IDE397 (MAT2A) and AMG 193 (PRMT5MTA) combination in patients with MTAP-deletion solid tumors.
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Amgen-sponsored Phase 1/2 clinical trial (NCT 05975073) has an estimated enrollment of approximately 180 patients with solid tumors having MTAP deletion, with a planned expansion focus in NSCLC, to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of the combination.
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IDE397 monotherapy Phase 2 expansion enrolling patients with MTAP-deletion NSCLC, bladder, esophageal and gastric cancers.
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Preliminary clinical data for IDE397 shows responses in multiple MTAP-deletion high-priority tumor types based on experience across several patients in the early phase of the monotherapy dose expansion. These include an earlier-reported unconfirmed partial response which was subsequently confirmed (~47% tumor reduction) in one of the high-priority tumor types and an additional observed~33% tumor reduction in NSCLC as measured by CT-PET.
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International site activation ongoing in support of monotherapy expansion, including in Europe and Asia, to enhance patient enrollment in high priority MTAP-deletion tumors.
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Presented preclinical efficacy data and supporting data at the 2023 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), or AACR (Free AACR Whitepaper) 2023:
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Preclinical data for the IDE397 and AMG 193 combination in a NSCLC MTAP-null CDX model showed complete responses following approximately 30 days of combination treatment, at doses below the maximally efficacious preclinical dose for each of IDE397 and AMG 193. The complete responses were durable from approximately study-day 40 to study-day 100. The IDE397 and AMG 193 combination was well
Exhibit 99.1

tolerated, with no observed body weight loss through the approximate 30 days of combination treatment.
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Preclinical efficacy data at AACR (Free AACR Whitepaper) 2023 showing deep and durable anti-tumor efficacy and PD responses for IDE397 in combination with representative MTA-cooperative PRMT5 inhibitors in NSCLC MTAP-null CDX models, and for one representative compound, also in a pancreatic MTAP-null CDX model.
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Results of gene expression analysis of hallmark pathways, alternative splicing analysis and retained intron analysis collectively demonstrate that combined pharmacological inhibition of MAT2A and PRMT5 deepens the biological response through maximal pathway suppression. The enhanced combination effect was observed selectively in MTAP-null relative to MTAP wild-type models.
IDE161—PARG Inhibitor in Tumors with Homologous Recombination Deficiency

IDEAYA is clinically evaluating its poly (ADP-ribose) glycohydrolase (PARG) inhibitor development candidate, IDE161, in a Phase 1/2 clinical trial, designated as IDE161-001, in patients having tumors with homologous recombination deficiencies (HRD), including BRCA1 and BRCA2, and potentially other alterations, in solid tumors such as breast cancer or ovarian cancer. PARG is a novel, mechanistically distinct target in the same clinically validated biological pathway as poly (ADP-ribose) polymerase (PARP).

IDEAYA owns or controls all commercial rights to IDE161 and its PARG program, subject to certain economic obligations pursuant to its exclusive, worldwide license with Cancer Research UK and University of Manchester. Highlights:

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Ongoing enrollment of patients having tumors with HRD into the dose escalation portion of the Phase 1/2 clinical trial
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Planned expansion cohorts will include ER+, Her2- HRD breast cancer patients, which represent approximately 10% to 14% of breast cancer patients, as well as HRD ovarian cancer patients, and a basket expansion cohort of other solid tumors with HRD.
Pol Theta Helicase Inhibitor Development Candidate in Tumors with HRD

GSK101 (IDE705) – Pol Theta Helicase Inhibitor in Tumors with HR Mutations

GSK101 (IDE705) is targeting Pol Theta Helicase for solid tumors with homologous recombination (HR) mutations, such as BRCA, or homologous recombination deficiency (HRD). IDEAYA and GSK collaborated on preclinical research and, following selection of GSK101 as the development candidate, GSK is leading clinical development for the Pol Theta program. Highlights:

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Submitted IND and anticipating clearance by U.S. FDA in Q3 2023 to enable a GSK-sponsored Phase 1/2 clinical trial to evaluate GSK101 in combination with niraparib for patients having solid tumors with HR mutations, such as BRCA, or HRD.
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Eligible to receive $7 million milestone payment from GSK upon IND clearance, and potential additional $10 million upon initiation of Phase 1 clinical dose expansion
Exhibit 99.1

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Observed tumor regressions in preclinical combination studies of Pol Theta Helicase DC with niraparib in multiple in vivo PDX and CDX HRD models
WRN Inhibitor in Tumors with High Microsatellite Instability

IDEAYA and GSK are collaborating on ongoing preclinical research for an inhibitor targeting Werner Helicase for tumors with high microsatellite instability (MSI), and GSK will lead clinical development for the Werner Helicase program. Highlights:

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Targeting selection of a Werner Helicase development candidate in H2 2023, in collaboration with GSK
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Potential to receive $3 million milestone payment from GSK in connection with IND-enabling studies and up to an additional $17 million aggregate through early Phase 1
Next-Generation Precision Medicine Pipeline Programs

IDEAYA has initiated early preclinical research programs focused on pharmacological inhibition of several new targets, or NTs, for patients with solid tumors characterized by defined biomarkers based on genetic mutations and/or molecular signatures. These research programs have the potential for discovery and development of first-in-class or best-in-class therapeutics. IDEAYA owns or controls all commercial rights in its next generation NT programs.

Corporate Updates

IDEAYA’s net losses were $27.9 million and $23.6 million for the three months ended June 30, 2023 and March 31, 2023, respectively. As of June 30, 2023, the company had an accumulated deficit of $287.0 million.

As of June 30, 2023, IDEAYA had cash, cash equivalents and marketable securities of $510.1 million. These funds are anticipated to fund IDEAYA’s planned operations into 2027 and support the company’s activities through potential achievement of multiple preclinical and clinical milestones across multiple programs.

On April 27, 2023, IDEAYA announced the closing of an underwritten public offering of shares of IDEAYA common stock and of pre-funded warrants to purchase IDEAYA common stock, resulting in aggregate net proceeds of approximately $188.7 million, after deducting underwriting discounts and commissions and other offering expenses.

On June 26, 2023, the company filed a new Form S-3 Registration Statement as an automatic shelf registration statement and as a "well-known seasoned issuer" as defined in Rule 405 under the Securities Act of 1933, following the lapse of the prior Form S-3 Registration Statement filed under the Securities Act of 1933 and effective as of June 10, 2020.

On June 26, 2023, IDEAYA entered into a new Open Market Sales Agreement, or June 2023 Sales Agreement, with Jefferies relating to an at-the-market offering program under which the company may offer and sell, from time to time at its sole discretion, shares of its common stock, par value $0.0001 per share, having aggregate gross proceeds of up to $250.0 million through Jefferies as sales agent. During the reporting period for the quarter ended June 30, 2023, IDEAYA sold an aggregate of 10,124 shares of our common stock for aggregate net

Exhibit 99.1

proceeds of $0.2 million at a weighted average sales price of approximately $23.52 per share under the at-the-market offering pursuant to the June 2023 Sales Agreement with Jefferies as sales agent. As of June 30, 2023, $249.8 million of common stock remained available to be sold under the at-the-market facility associated with the June 2023 Sales Agreement.

Subsequent to the reporting period for the quarter ended June 30, 2023, the company sold an aggregate of 76,421 shares of our common stock for aggregate net proceeds of $1.7 million at a weighted average sales price of approximately $23.53 per share under the at-the-market offering pursuant to the June 2023 Sales Agreement with Jefferies as sales agent.

IDEAYA’s updated corporate presentation is available on its website, at its Investor Relations page: View Source

Financial Results

As of June 30, 2023, IDEAYA had cash, cash equivalents and short-term marketable securities totaling $510.1 million. This compared to cash, cash equivalents and short-term and long-term marketable securities of $351.2 million as of March 31, 2023. The increase was attributable to net proceeds of $188.7 million from the sale of shares of IDEAYA common stock and pre-funded warrants to purchase IDEAYA common stock in connection with the underwritten public offering, offset by cash used in operations.

Collaboration revenue for the three months ended June 30, 2023 totaled $3.5 million compared to $7.9 million for the three months ended March 31, 2023. Collaboration revenue was recognized for the performance obligations satisfied through June 30, 2023 under the GSK Collaboration Agreement.

Research and development (R&D) expenses for the three months ended June 30, 2023 totaled $29.2 million compared to $27.9 million for the three months ended March 31, 2023. The increase was primarily due to higher clinical trial expenses.

General and administrative (G&A) expenses for the three months ended June 30, 2023 totaled $7.1 million compared to $6.3 million for the three months ended March 31, 2023. The increase was primarily due to higher audit and tax fees.

The net loss for the three months ended June 30, 2023 was $27.9 million compared to the net loss of $23.6 million for the three months ended March 31, 2023. Total stock compensation expense for the three months ended June 30, 2023 was $4.7 million compared to $3.7 million for the three months ended March 31, 2023.

On August 10, 2023 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported financial results and business highlights for the second quarter of 2023 (Press release, Hookipa Biotech, AUG 10, 2023, View Source [SID1234634191]).

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"A key highlight was reporting our positive preliminary Phase 2 data on HB-200 in combination with pembrolizumab for advanced head and neck cancer. We continue to collect evidence that our novel arenaviral technology may help address unmet needs in cancer, with greater objective response rates than the current standard of care and clear trends towards duration of clinical benefit," said Joern Aldag, Chief Executive Officer at HOOKIPA Pharma. "We’re pleased investors also acknowledged the strength of our data with the $50 million capital raise. We’re now focused on preparing for the randomized trial of HB-200 in combination with pembrolizumab to start in the first half of 2024, as well as continuing to advance our clinical programs and diverse pipeline overall."

Quarter highlights

Oncology

In May, HOOKIPA announced positive preliminary Phase 2 data on HB-200 in combination with pembrolizumab in patients with recurrent/metastatic Human Papillomavirus 16-positive (HPV16+) head and neck cancers. Data from the ongoing study (NCT04180215) showed a 43 percent objective response rate with HB-200 in combination with pembrolizumab in checkpoint inhibitor (CPI)-naïve patients, doubling the response rate for pembrolizumab alone. HOOKIPA plans to share more data at a medical conference later this year and is preparing to start a randomized trial of HB-200 with pembrolizumab in the 1st-line setting in 2024.

In June, HOOKIPA presented a trial-in-progress presentation at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on its ongoing Phase 1/2 study (NCT05553639) of HB-300 for the treatment of advanced prostate cancer. HB-300 is an arenaviral immunotherapy that targets two well-defined self-antigens of prostate cancer, prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA). The ability to break immune tolerance and mount a strong T cell response against these self-antigens remains an unmet need in prostate cancer. Preclinical studies have demonstrated the ability of HOOKIPA’s arenaviral technology to break tolerance and elicit a strong immune response against self-antigens. Initial safety, tolerability and immunogenicity data from the ongoing Phase 1 study of HB-300 are expected in the first half of 2024.

HOOKIPA’s HB-700 program, in collaboration with Roche, is progressing to an expected Investigational New Drug (IND) application filing in the first half of 2024. HB-700 is a novel arenaviral immunotherapy for KRAS-mutated cancers, including lung, pancreatic and colon cancers.

Infectious disease

In May, HOOKIPA announced that the first participant had been dosed in a Gilead’s Phase 1 clinical trial (NCT05770895) of HB-400, an investigational therapeutic vaccine for chronic hepatitis B using HOOKIPA’s arenaviral platform. HB-400 is one of two independent development programs in HOOKIPA’s collaboration and license agreement with Gilead Sciences, Inc. Gilead is solely responsible for further development and commercialization of the hepatitis B product candidate.

HOOKIPA’s HB-500 program, partnered with Gilead, is progressing towards an anticipated IND filing in the second half of 2023 and is expected to commence a Phase 1 clinical trial in 2024. HB-500 is a novel arenaviral vaccine that will be assessed as part of a potential functional curative regimen for HIV.

Corporate

In June, HOOKIPA completed a $50 million public offering of common stock and non-voting convertible preferred stock. The net proceeds will support the randomized study of HB-200 in combination with pembrolizumab, as well as other clinical programs.

In August, the board of directors approved an exchange offer to eligible employees, excluding executive officers, members of the board of directors and members of HOOKIPA’s scientific advisory board, for certain underwater stock options. A total of 627,632 options with an exercise price per share greater than $6.50 will be eligible for exchange into up to a total of 315,505 new stock options with modified terms and an exercise price per share equal to the closing price on the grant date of the new option, but not less than $1.00. The exchange offer shall be made pursuant and subject to a tender offer statement, including an offer to exchange, to be filed with the Securities and Exchange Commission (SEC) today, which shall be the only basis for such offer.

Upcoming Milestones

Phase 2 HB-200 in HPV16+ head and neck cancers
1st-line follow-up data in combination with pembrolizumab: H1 2024
2nd+-line follow-up data in combination with pembrolizumab: Q1 2024
Start of 1st-line randomized study in combination with pembrolizumab:
H1 2024 (Fast Track designation)
Phase 1 HB-300 in prostate cancer
Preliminary safety and immunogenicity data: H1 2024
HB-700 in KRAS-mutated cancers: IND filing H1 2024
HB-400 in hepatitis B: to be determined by Gilead
HB-500 in HIV: IND filing 2023

Second Quarter 2023 Financial Results
Cash Position: HOOKIPA’s cash, cash equivalents and restricted cash as of June 30, 2023 was $136.0 million compared to $113.4 million as of December 31, 2022. The increase was primarily attributable to funds resulting from the follow-on financing in June 2023, partly offset by cash used in operating activities.

Revenue: Revenue was $2.7 million for the three months ended June 30, 2023 and for the three months ended June 30, 2022. A decrease of cost reimbursements received under the Restated Gilead Collaboration Agreement, was largely offset by higher partial recognition of the upfront and milestone payments under the Gilead collaboration and Roche collaboration.

Research and Development Expenses: HOOKIPA’s research and development expenses were $19.7 million for the three months ended June 30, 2023, compared to $16.1 million for the three months ended June 30, 2022. The primary drivers of the increase in research and development expenses by $3.6 million compared to the three months ended June 30, 2022 were higher clinical study expenses for our HB-200 and HB-300 programs as well as increased spending for our Gilead and Roche partnered programs.

General and Administrative Expenses: General and administrative expenses amounted to $4.4 million for the three months ended June 30, 2023, compared to $5.0 million for the three months ended June 30, 2022. The decrease was primarily due to a decrease in other expenses, and a decrease in personnel-related expenses, partially offset by an increase in professional and consulting fees. The decrease in personnel-related expenses resulted from decreased stock compensation expenses, partially offset by a growth in headcount along with increased salaries in our general and administrative functions as well as expenses for contractors.

Net Loss: HOOKIPA’s net loss was $18.0 million for the three months ended June 30, 2023, compared to a net loss of $16.4 million for the three months ended June 30, 2022. This increase was primarily due to an increase in research and development expenses.

On August 10, 2023 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported the United States Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to the Company’s lead drug candidate, REQORSA Immunogene Therapy (quratusugene ozeplasmid), for the treatment of small cell lung cancer (SCLC) (Press release, Genprex, AUG 10, 2023, View Source [SID1234634190]).

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In addition to ODD for the treatment of SCLC, in June 2023, the FDA granted Fast Track Designation (FTD) for REQORSA Immunogene Therapy, in combination with Genentech, Inc’s Tecentriq in patients with extensive-stage small cell lung cancer (ES-SCLC) who did not develop tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment. With ES-SCLC, the cancer has spread from one lung to the other, or to other parts of the body. Extensive-stage is the most common type of SCLC. FDA has also granted Genprex FTD for two other indications of REQORSA Immunogene Therapy, including REQORSA in combination with Tagrisso for non-small cell lung cancer (NSCLC) in patients who have progressed after Tagrisso treatment, and REQORSA in combination with Keytruda for NSCLC in patients who have progressed after Keytruda treatment.

"We are excited to receive Orphan Drug Designation from the FDA for REQORSA for patients with SCLC," said Rodney Varner, President, Chairman and Chief Executive Officer at Genprex. "This FDA Orphan Drug Designation in combination with our recently received FDA Fast Track designation underscores the great need for better treatment options for patients with SCLC, ES-SCLC and NSCLC. We look forward to initiating the Acclaim-3 clinical trial expected in the fourth quarter of 2023 in order to bring hope of an effective new therapy to patients suffering with this life-limiting cancer."

The FDA grants ODD status to investigational therapies being developed to treat, diagnose, or prevent a rare disease or condition affecting fewer than 200,000 people in the United States. Further, ODD provides benefits to drug developers, including assistance in the drug development process, tax credits for qualified trials, waiver of certain FDA fees, and potential for seven years of post-approval marketing exclusivity.

Genprex’s method of treating cancer is to reexpress tumor suppressor genes in cancers. Tumor suppressor genes are deleted or inactivated early in the process of cancer development. REQORSA contains a plasmid that expresses a tumor suppressor gene protein called TUSC2. Virtually 100% of small cell lung cancers have reduced or no TUSC2 protein expression, and 41% completely lack TUSC2 protein expression. Pre-clinical studies in mice suggest that re-expressing the TUSC2 protein may lead to clinical efficacy. ES-SCLC has a very poor prognosis, with a median progression free survival (PFS) of only 5.2 months. Importantly, median PFS for patients receiving Tecentriq as maintenance therapy is only 2.6 months from the start of maintenance treatment, so there is a great need for improvement in maintenance therapy.

About Acclaim-3 Clinical Trial

The Acclaim-3 clinical trial is a Phase 1/2 open-label, dose escalation and clinical response study of maintenance therapy evaluating REQORSA in combination with Tecentriq in patients with ES-SCLC who did not develop tumor progression after receiving Tecentriq and chemotherapy as initial standard treatment.

Patients in the Acclaim-3 clinical trial will be enrolled after receiving initial treatment with 3-4 cycles of carboplatin, etoposide, and Tecentriq, and achieving complete response, partial response or stable disease. They will then receive treatment with REQORSA and Tecentriq as maintenance therapy every 21 days until disease progression.

The Phase 1 dose escalation portion of the Acclaim-3 clinical trial is expected to enroll up to 12 patients at 3-5 U.S. clinical sites to determine the Maximum Tolerated Dose (MTD). If no dose limiting toxicities occur during Phase 1, then the highest dose evaluated will be the Recommended Phase 2 Dose. The Phase 2 portion of the study will then enroll approximately 50 patients at 5-10 sites. Patients will be treated with REQORSA and Tecentriq until disease progression or unacceptable toxicity is experienced.

The primary endpoint of the Phase 2 portion of the trial is to determine the 18-week progression-free survival rate from the time of the start of maintenance therapy with REQORSA and Tecentriq in patients with ES-SCLC. Patients will also be followed for survival. A Phase 2 futility analysis will be performed after the 25th patient enrolled and treated reaches 18 weeks of follow up.