On November 10, 2021 Clarity Pharmaceuticals (ASX: CU6) ("Clarity" or the "Company"), an Australian-based clinical stage radiopharmaceutical company developing next-generation products to address the growing need in oncology, reported that it has completed recruitment for the initial dosimetry phase of its US-based SECuRE clinical trial (NCT04868604)1 investigating SAR-bisPSMA Targeted Copper Theranostics (TCT) in patients with metastatic castrate-resistant prostate cancer (mCRPC) (Press release, Clarity Pharmaceuticals, NOV 10, 2021, View Source [SID1234595055]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The SECuRE trial is a Phase I/IIa theranostic trial for identification and treatment of prostate specific membrane antigen (PSMA)-expressing mCRPC using TCT. 64Cu SAR-bisPSMA is used to visualise PSMA expressing lesions and select candidates for subsequent 67Cu SAR-bisPSMA therapy. The initial dosimetry phase utilised 64Cu SAR-bisPSMA to determine biodistribution and dosimetry of the products in humans. The SECuRE trial is a multi-centre, single arm, dose escalation study with a cohort expansion planned for up to 44 patients in the US. The aim of this trial is to determine the safety and efficacy of 67Cu SAR-bisPSMA as a therapy.

Clarity’s Executive Chairman, Dr Alan Taylor, commented, "We are very pleased to have quickly and successfully completed the recruitment for the initial dosimetry phase of the SECuRE trial in mCRPC using our optimised next-generation PSMA agent, SAR-bisPSMA, and look forward to progressing through the safety review shortly. We are excited to move quickly to the therapy phase with 67Cu SAR-bisPSMA at all seven clinical sites selected for this trial in the US.

"The PET imaging data acquired in the SECuRE trial to date looks very promising and the images confirm our excellent preclinical results of high tumour targeting and retention whilst seeing washout in other tissues. We are excited with the comparison to the standard of care bone scan (the recommended modality for bone imaging in clinical trials according to the Prostate Cancer Clinical Trials Working Group 3), indicating that 64Cu SAR-bisPSMA is able to visualise bone involvement. This further supports the emerging evidence of increased sensitivity and specificity of PSMA PET tracers for detecting micrometastatic disease compared to conventional imaging. With the recently updated US National Comprehensive Cancer Network Guidelines now allowing FDA-approved PSMA PET agents to be used as an alternative to conventional imaging, we are really looking forward to progressing this product quickly through clinical trials with the added value of manufacturing, logistics and patient benefits that 64Cu provides.

"Our TCT platform uniquely uses the same chemical entity for both diagnosis and therapy, leading to high accuracy and high precision, and highlights the benefits of generating 64Cu imaging data from 1h to 72h after administration to help determine the suitability of treatment with 67Cu. We strongly believe SAR-bisPSMA will be an important pillar in the next generation of radiopharmaceuticals, with blockbuster potential both diagnostically and therapeutically. The central manufacture, logistical and treatment advantages of TCT associated with using the isotope pairing of 64Cu and 67Cu in large patient populations such as prostate cancer will provide significant benefits to both patients and clinicians in comparison to current products in the market."

Dr Luke Nordquist, CEO, Urologic Medical Oncologist at the Urology Cancer Center and GU Research Network in Omaha, Nebraska, who treated patients in the initial dosimetry phase of the trial, commented, "I am very impressed with the data from the initial dosimetry phase and we look forward to progressing the SECuRE trial into the therapy phase and further validating the benefits of the 64Cu SAR-bisPSMA and 67Cu SAR-bisPSMA products for both clinicians and patients. Current standard of care SPECT imaging agents don’t have the resolution of the new PET agents, however the new PET agents rely on radionuclides with very short half-lives such as 18F and 68Ga, which limits their availability and utilisation. Having access to centrally manufactured PET imaging products with a more suitable half-life, such as 64Cu, will significantly improve patient care and address the current backlog of patients waiting for critical imaging scans. Importantly, the potential for improved prostate cancer diagnosis and treatment will have significant benefits for prostate cancer patients."

Dr Taylor said: "The future of radiopharmaceuticals is here, where patient care is not dictated by the limited half-life of the isotope, and instead focuses on what is important for the patient, clinician and treating staff – safety, efficacy, access and flexibility. The further expansion of radiopharmaceuticals into more indications, with greater utilisation from a broad spectrum of clinicians, will be dependent upon centralised, large volume and simple supply logistics of isotopes and ready-to-use radiopharmaceuticals whilst focusing on long-term environmental impacts of the supply chain. Clarity’s ability to centrally manufacture and broadly distribute large volumes of copper-based products, without long lived radioactive waste products or dependance on nuclear reactors, will be a significant factor in addressing large markets in a sustainable manner. To that end, we are very excited to be quickly advancing our TCT platform and numerous TCT products through clinical trials to generate compelling clinical data and move closer to achieving our ultimate goal of developing better treatments for children and adults with cancer."

This announcement has been authorised for release by the Executive Chairman.

About Prostate Cancer
Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death worldwide2. In 2021, the National Cancer Institute estimated 248,530 new cases of prostate cancer in the US and around 34,130 deaths from the disease3. Annually, there are around ~34,000 men in the US who are diagnosed with mCRCP4, ~90% of whom have tumours which express PSMA5.

References
gov Identifier: NCT04868604 View Source
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries View Source
American Cancer Society, Cancer Statistics Center, View Source!/cancer-site/Prostate
American Cancer Society, Cancer Statistics Center, View Source!/cancer-site/Prostate
A. Silver, I. Pellicer, W. R. Fair, W. D. Heston and C. Cordon-Cardo 1997. "Prostate-specific membrane antigen expression in normal and malignant human tissues." Clinical Cancer Research. vol. 3, 81-85, January 1997

On November 10, 2021 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company enabled by its proprietary synthetic lethality approach to the discovery and development of novel therapeutics, reported financial results for the third quarter ended September 30, 2021 (Press release, Repare Therapeutics, NOV 10, 2021, View Source [SID1234595054]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased with the progress we’ve made this quarter in our Phase 1 part of the RP-3500 program, including the comprehensive safety data and emerging evidence of activity from the TRESR study which was part of the featured oral presentation at the AACR (Free AACR Whitepaper)-NCI-EORTC conference this year," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "The findings continue to suggest RP-3500 may have broad clinical efficacy in tumors with diverse genetic alterations and provides further clinical proof of concept and validation of our SNIPRx platform. We look forward to providing updates in the future on the potential of RP-3500, both as a monotherapy and in combination with PARP inhibitors."

Third Quarter 2021 Review and Operational Updates:

Announced initial monotherapy clinical data from Phase 1/2 TRESR study of RP-3500 in patients with solid tumors at the AACR (Free AACR Whitepaper)-NCI-EORTC conference
Early data showed RP-3500 appears safe and well tolerated. The most common treatment emergent adverse events in any of the 101 patients treated, expectedly, was grade 1-2 anemia, with only 21.8% of all patients experiencing Grade 3 anemia (no Grade 4). There were no discontinuations related to RP-3500 emergent adverse events and dose interruptions, and reductions or red blood cell transfusions were infrequent on the recommended 3 days on/4 days off weekly regimen.
Recommended Phase 2 dose and schedule for further monotherapy RP-3500 evaluation was determined to be 160mg, taken weekly for 3 days on and 4 days off. This schedule assures repeated weekly exposure to RP-3500 at an efficacious dose. The Grade 3 anemia rate at this schedule overall was only 14.5%.
Antitumor activity, defined as RECIST based objective responses, was observed in patients with tumors harboring SNIPRX predicted genomic alternations at doses >100mg (ATM, CDK12, BRCA1, BRCA2, RAD51C), across multiple tumor types and included patients after PARP inhibitor failure. Meaningful clinical benefit was observed in 49% of 69 patients with available scans. Those include 12 patients with tumor responses per established international efficacy criteria, 14 patients with ongoing stable disease for at least 16 weeks and an additional 8 patients with stable disease who only had two radiological evaluations, but had demonstrated significant decreases in tumor markers or initial tumor shrinkage of less than 30%. Promising deep molecular responses in circulating tumor DNA (ctDNA) for tumors with STEP2 genomic alterations were observed in a subset of patients available for serial ctDNA analysis.
Final readouts from patients enrolled in the monotherapy arm of the TRESR trial, as well as initial data from the combination arm testing RP-3500 together with PARP inhibitors, are expected in 2022.

Raised Gross Proceeds of $101.2 Million in Upsized Follow-on Public Offering
In November 2021, the Company announced the closing of an upsized unwritten follow-on public offering yielding aggregate gross proceeds of approximately $101.2 million, or net proceeds of approximately $93.9 million, after deducting underwriting commissions and estimated offering expenses of $1.2 million payable by us. All of the shares in the offering were offered by Repare Therapeutics.
Appointed Thomas Civik to Board of Directors as new Chairman
In September 2021, the Company appointed Thomas Civik to its Board of Directors as its Chairman. He replaced Jerel Davis, Ph.D., who remains a Board member.
Mr. Civik was most recently President and CEO of Five Prime Therapeutics until its $1.9 billion acquisition by Amgen in April 2021. He has over 25 years of leadership and commercial experience at various companies including Foundation Medicine and Genentech.
Achieved $0.9 million (¥100 million) research trigger pursuant to the terms of its research services, license and collaboration agreement with Ono Pharmaceutical Co., Ltd
On October 13, 2021, upon the occurrence of a specified research trigger, the Company became eligible to receive a portion, amounting to ¥100 million ($0.9 million), of the research service payments provided for in its research services, license and collaboration agreement with Ono Pharmaceutical Co., Ltd., or Ono, ("Ono Agreement") for the research of potential product candidates targeting Polθ. Furthermore, on October 29, the Company and Ono entered into an amendment to the Ono Agreement whereby the Research Term, as defined in the Ono Agreement, was extended by one year.
Third Quarter 2021 Financial Results:

Cash and cash equivalents, restricted cash and marketable securities: Cash and cash equivalents, restricted cash and marketable securities as of September 30, 2021 were $268.2 million, exclusive of the proceeds from the follow-on public offering.
Research and development expenses, net of tax credits (Net R&D): Net R&D expenses were $25.4 million and $62.1 million for the three- and nine-month periods ended September 30, 2021, respectively, as compared to $10.1 million and $27.7 million for the three- and nine-month periods ended September 30, 2020, respectively. The increase in R&D expenses for the three and nine-month periods were primarily due to increases in development costs related to the Company’s RP-3500 and RP-6306 programs, as well as increases in personnel related expenses, including share-based compensation.
General and administrative (G&A) expenses: G&A expenses were $6.6 million and $18.6 million for the three and nine-month periods ended September 30, 2021, respectively, as compared to $4.0 million and $9.6 million for the three and nine-month periods ended September 30, 2020, respectively. The increase in G&A expenses for the three and six-month periods were due to personnel related costs, including share-based compensation, and D&O insurance which increased as a result of the Company’s IPO in June 2020.
Net loss: Net loss was $30.9 million, or $0.83 per share and $78.6 million, or $2.12 per share, in the three and nine-month periods ended September 30, 2021, respectively, and $13.8 million, or $0.37 per share and $38.2 million, or $2.63 per share in the three and nine-month periods ended September 30, 2020, respectively.
About Repare Therapeutics’ SNIPRx Platform

Repare’s SNIPRx platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic profile of their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx screening, in order to selectively target those tumors in patients most likely to achieve clinical benefit from resulting product candidates.

On November 10, 2021 Werewolf Therapeutics, Inc. (the "Company" or "Werewolf") (Nasdaq: HOWL), an innovative biopharmaceutical company pioneering the development of conditionally activated therapeutics engineered to stimulate the body’s immune system for the treatment of cancer, reported financial results for the quarter ended September 30, 2021 (Press release, Werewolf Therapeutics, NOV 10, 2021, View Source [SID1234595053]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Werewolf Therapeutics continues to make significant progress advancing and executing across our pipeline and we are on track to file INDs for our two lead INDUKINE product candidates, WTX-124 and WTX-330, in the first half of 2022," said Daniel J. Hicklin, Ph.D., President and Chief Executive Officer of Werewolf. "We have also achieved several important corporate milestones, including the announcement of our clinical trial collaboration and supply agreement with Merck to evaluate WTX-124 in combination with KEYTRUDA."

Merck Collaboration: In August 2021, Werewolf announced its entry into a clinical trial collaboration agreement with Merck, known as MSD outside the United States and Canada, to evaluate WTX-124, a systemically-delivered, conditionally activated Interleukin-2 (IL-2) INDUKINE product candidate, in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 (programmed death receptor-1) therapy. The planned clinical trial will be conducted by Werewolf and is designed to evaluate the safety and preliminary efficacy of WTX-124 as a monotherapy and in combination with KEYTRUDA in patients with solid tumors.

Expanded the Board of Directors: In October 2021, Werewolf appointed Meeta Chatterjee, Ph.D., as a member of the Board of Directors. Dr. Chatterjee brings over 30 years of broad strategic and operational experience in pharmaceutical research and development, mergers and acquisition evaluation, in-licensing, and externalization activities.

Upcoming preclinical presentations at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) being held November 10-14, 2021 in Washington, DC: Werewolf will present posters on its lead programs WTX-124 (Poster #718), WTX-330 (Poster #715) and WTX-613 (Poster #723) describing the design and preclinical evaluation of Werewolf’s IL-2, IL-12 and IFN-a INDUKINE molecules.

Third Quarter 2021 Financial Highlights

Cash position: As of September 30, 2021, cash and cash equivalents were $170.4 million, compared to $92.6 million as of December 31, 2020. The increase was primarily due to the receipt of $109.2 million in net proceeds from the initial public offering completed in May 2021, offset by operating expenses incurred during the period. Given the strength of its balance sheet, Werewolf expects its existing cash and cash equivalents to enable the funding of its operating expenses and capital expenditure requirements through at least the second quarter of 2023.

Research and development expenses: Research and development expenses were $9.8 million for the third quarter of 2021, compared to $4.8 million for the same period in 2020. The increase in research and development expenses was primarily due to increased manufacturing, contract research organization, and personnel expenses incurred to advance the Company’s product candidates WTX-124, WTX-330 and WTX-613 and expand research and development activities.

General and administrative expenses: General and administrative expenses were $4.0 million for the third quarter of 2021, compared to $1.2 million for the same period in 2020. The increase in general and administrative expenses was primarily due to increased personnel, professional services, and other operating costs attributable to operating as a public company.

Net loss: Net loss was $13.8 million for the third quarter of 2021, compared to $6.1 million for the same period in 2020.

On November 10, 2021 CureVac N.V. (Nasdaq: CVAC), a global biopharmaceutical company developing a new class of transformative medicines based on messenger ribonucleic acid ("mRNA"), reported promising data from the completed dose-escalation part of the Phase 1 clinical trial of CV8102, the company’s lead oncology candidate (Press release, CureVac, NOV 10, 2021, View Source [SID1234595052]). The data support the hypothesis that local injection of the RNA immuno-modulator into a single tumor lesion is able to induce a systemic response leading to immune attack against both injected and non-injected tumors. Extensive analysis of immune cell activation shows efficient stimulation of the immune system characterized by the induction of interferon alpha and interferon gamma signaling pathways. Serial tumor biopsies from individual patients demonstrated increased infiltration of tumor-fighting T cells in the microenvironment of injected as well as non-injected tumors. The study focuses on patients with advanced cutaneous melanoma, adenoid cystic carcinoma and squamous cell carcinoma of the skin or head and neck, treated with CV8102 alone and in combination with anti-PD-1 antibodies. The data are being presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference, held in Washington, D.C., and virtually from November 10–14, 2021.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The preliminary data from the Phase 1 dose escalation part of this study allow a much deeper understanding of the promising biologic effects of CV8102 observed in several patients," said Dr. Klaus Edvardsen, Chief Development Officer at CureVac. "CV8102 is designed to mimic a viral infection of the injected tumor. This potentially leads to a broad activation of tumor-specific T cells, which can kill tumor cells at the injected but also at distant sites. We expect that the data will be supplemented by upcoming results of the expansion study, which will provide further insight into which patients are more likely to experience a clinical response to CV8102."

An expansion part of the Phase 1 study, initiated in February and fully recruited in October 2021, aims to confirm the safety, tolerability and efficacy of CV8102 at the recommended 600μg dose in patients with advanced melanoma. The study involves 40 trial participants, with 10 in the single-agent cohort and 30 in the combination cohort. Data from the expansion part of the study is expected in the second half of 2022.

The dose-escalation part of the study included a total of 58 patients, 33 of which were treated in the in the single-agent cohort and 25 in the combination cohort. Data presented in September at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) conference found that as of the cutoff date of June 21, 2021, in the single-agent CV8102 dose-escalation cohort, one patient with a complete response and two patients with a partial response were observed. In addition, 12 patients experienced stable disease. In the PD-1 combination dose-escalation cohort, one PD-1 refractory melanoma patient experienced a partial response while three patients experienced stable disease.

About CV8102 and the Phase 1 Clinical Trial

CV8102 is a single-stranded non-coding RNA optimized to maximize activation of cellular receptors that normally detect viral pathogens entering the cells, such as toll-like receptors 7 and 8 (TLR7/8), and retinoic acid inducible gene I (RIG-I), mimicking a viral infection of the tumor. CV8102 is designed to recruit and activate antigen-presenting cells at the site of injection to present tumor antigens released from tumor cells to T cells in the draining lymph node. This potentially leads to activation of tumor-specific T cells, which can kill tumor cells at the injected site, but also at distant non-injected tumor lesions or metastases.

The Phase 1, open-label, dose escalation and expansion study of CV8102 is fully recruited and includes patients with advanced melanoma, cutaneous squamous cell carcinoma, squamous cell carcinoma of head and neck or adenoid cystic carcinoma. The primary objective of the study is to assess safety and tolerability of CV8102.The dose escalation part tests escalating doses of single-agent CV8102 and CV8102 in combination with licensed anti-PD-1 antibodies in the range of 25-900µg. The expansion part of the study focuses on patients with advanced melanoma treated with a recommended dose of 600µg.

On November 10, 2021 Immunocore Holdings plc (Nasdaq: IMCR), a late-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 and autoimmune disease, reported its financial results for the quarter and nine months ended September 30, 2021 and provides a business update (Press release, Immunocore, NOV 10, 2021, View Source [SID1234595051]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Immunocore’s recent and third quarter highlights include the acceptance of tebentafusp regulatory submissions in the US, EU and UK; the publication of Phase 3 tebentafusp data in the New England Journal Medicine; and the continued dose escalation of MAGE-A4 and PRAME targeting ImmTACs with data to be presented from IMC-C103C targeting MAGE-A4 at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress in December of this year (ESMO IO Congress).

Bahija Jallal, Chief Executive Officer of Immunocore, said: "We continue to be encouraged by the interest in our tebentafusp data in metastatic uveal melanoma, including the publication of our Phase 3 data in the New England Journal of Medicine. We have now activated our early access program in fourteen countries and have treated over 150 patients with metastatic uveal melanoma over the last six months. As we advance our ImmTAC programs in other solid tumors, we look forward to continuing to update on our progress at upcoming medical meetings."

Third Quarter 2021 Highlights (including post-period)

Tebentafusp

Earlier this month, the Company presented new clinical data from the metastatic uveal melanoma (mUM) tebentafusp monotherapy program and a Phase 1b study of tebentafusp in combination with durvalumab (anti-PDL1) and/or tremelimumab (anti-CTLA4) in metastatic cutaneous melanoma (mCM) in poster presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting. In a phase 1b trial in mCM of tebentafusp in combination with checkpoint inhibitors, in which the majority of patients had previously received prior anti-PD(L)1 treatments, the maximum target doses of tebentafusp (68 mcg) plus durvalumab (20 mg/kg) with and with/out tremelimumab (1 mg/kg) were tolerated in both doublet and triplet arms of the study. Preliminary evidence of tebentafusp clinical activity in mCM patients who had prior anti-PD(L)1 therapy, currently an unmet medical need, included 1-year overall survival (OS) rate of 76%. In mCM patients who were refractory (defined as best response of progressive disease) to prior anti-PD(L)1, the 1-year OS rate was 61%. In addition, the Company presented a new analysis of baseline gp100 protein tumor expression by immunohistochemistry of tumor biopsies from the phase 2 and phase 3 tebentafusp monotherapy mUM trials, where OS benefit was observed for both high and low gp100 protein tumor expression. Four additional posters depicting new analyses from tebentafusp in metastatic uveal melanoma, as well as the Company’s proprietary soluble TCR bispecific ImmTAC platform were also accepted for presentation at the upcoming SITC (Free SITC Whitepaper) 36th Annual Meeting and will be made available for on-demand viewing throughout the meeting.

In October, the Company announced an exclusive multi-regional agreement for Medison Pharma Ltd. to help seek regulatory authorization and commercialize Immunocore’s tebentafusp (IMCgp100), for the treatment of patients with mUM, in Canada, twenty markets across Central Eastern Europe and Israel. Under the agreement, Medison Pharma would also provide assistance with commercialization activities, assuming regulatory approval is received.

In the third quarter, the Australian Government Department of Health granted tebentafusp Orphan Drug Designation. Additionally, the Australian Government Department of Health has accepted the Marketing Application for tebentafusp in mUM, and the company (through the Adjutor Healthcare Party Ltd.) has also received a Priority Review of its application for approval.

In September, The New England Journal of Medicine (NEJM) published online data from the IMCgp100-202 Phase 3 randomized clinical trial in mUM where the OS Hazard Ratio (HR) in the intent-to-treat population favored tebentafusp, HR=0.51 (95% CI: 0.37, 0.71). The NEJM paper concluded that tebentafusp prolonged OS compared to investigator’s choice in previously untreated mUM.

In September, the Company presented new data and analysis from tebentafusp at the ESMO (Free ESMO Whitepaper) Congress. The findings presented in an oral presentation, by Alexander N. Shoushtari MD, medical oncologist at Memorial Sloan Kettering Cancer Center, demonstrated that 70% of evaluable patients had a reduction in circulating tumor DNA (ctDNA) by Week 9 and the degree of reduction was strongly associated with OS.

In September, the Company announced the United Kingdom’s Medicines and Healthcare products Regulatory Agency has accepted a MAA seeking the approval of tebentafusp for the treatment of patients with mUM.

In August, the U.S. Food and Drug Administration (FDA) accepted for review Immunocore’s BLA for tebentafusp. The FDA has granted Priority Review to the Company’s BLA submission, a designation for drugs which, if approved, may provide significant improvements in the safety and effectiveness of the treatment of serious conditions. Priority Review designation shortens the review period from the standard ten months to six months from the filing acceptance of the BLA, and therefore, there is a PDUFA target action date of February 23, 2022.

The FDA will review the BLA for tebentafusp under the Real-Time Oncology Review (RTOR) pilot program, an initiative of the FDA’s Oncology Center of Excellence designed to expedite the delivery of safe and effective cancer treatments to patients. Tebentafusp is also being reviewed under the FDA’s Project Orbis initiative, which enables concurrent review by the health authorities in partner countries that have requested participation. Previously, the FDA granted Breakthrough Therapy Designation to tebentafusp for the treatment of HLA-A*02:01-positive adult patients with unresectable or mUM. Over 150 patients have accessed tebentafusp through the global early access program across 14 countries.

In August, the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP), accepted the Company’s MAA. In July, the EMA agreed to the Company’s request for accelerated assessment of its MAA based on the determination that tebentafusp is a product of major interest for public health and therapeutic innovation. Accelerated assessment potentially reduces the time frame for the CHMP and Committee for Advanced Therapies to review the Company’s submitted MAA for advanced therapies. While the CHMP review period of a MAA can take up to 210 days, the accelerated assessment reduces the timeframe for review of the MAA to 150 days (excluding clock-stops).

IMC-C103C targeting MAGE-A4

In the third quarter, the Company continued to dose escalate IMC-C103C, an ImmTAC molecule targeting an HLA-A*02:01 MAGE-A4 antigen, in a first-in-human, Phase 1/2 dose escalation trial in patients with solid tumor cancers including non-small-cell lung cancer (NSCLC), gastric, head and neck, and ovarian. As of June 30, 2021, the Company has enrolled 39 patients in the Phase 1 study. Early pharmacodynamic data indicate that IMC-C103C monotherapy is demonstrating biological activity at the doses currently under evaluation. The Company plans to report the initial Phase 1 data at the ESMO (Free ESMO Whitepaper) IO Congress in December. Immunocore will also host an investor call on December 6th that will be accessible via the ‘Investor Relations’ section of the Company’s website.

IMC-F106C targeting PRAME

In the third quarter, the Company continued to dose escalate IMC-F106C, an ImmTAC molecule targeting an HLA-A*02:01 PRAME antigen, in a first-in-human, Phase 1/2 dose escalation trial in patients with multiple solid tumor cancers. PRAME is overexpressed in many solid tumors including NSCLC, SCLC, endometrial, ovarian, melanoma and breast cancers. As of June 30, 2021, the company has enrolled 23 patients in the Phase 1 study. Early pharmacodynamic data indicate that IMC-F106C monotherapy is demonstrating biological activity at the doses currently under evaluation. The Company plans to report the initial Phase 1 data in mid-2022.

IMC-I109V targeting HBV

In the third quarter, the Company continued to enroll patients in the IMC-I109V global Phase 1 single ascending dose trial. IMC-I109V is the first candidate in development using the Company’s immune‐mobilising monoclonal T cell receptors against virus (ImmTAV) platform to enter clinical trials. IMC-I109V targets a conserved Hepatitis B virus (HBV) envelope antigen and is being developed as a potential functional cure.

IMC-M113V targeting HIV

In the third quarter, the Company continued to advance IMC-M113V, an ImmTAV molecule target an HIV gag antigen bispecific TCR molecule. The Company’s HIV programs are funded by the Bill & Melinda Gates Foundation, and regulatory submission to enable clinical testing is anticipated in the second half of 2021.

Financial Results

Basic and diluted loss per share was £0.69 or $0.93 for the three months ended September 30, 2021 compared to an adjusted £0.72 for the three months ended September 30, 2020. Basic and diluted loss per share was £2.19 or $2.95 for the nine months ended September 30, 2021 compared to an adjusted £2.02 for the nine months ended September 30, 2020. Total operating loss for the three months ended September 30, 2021 was £31.0 million or $41.7 million compared to £23.4 million for the same period last year. Total operating loss for the nine months ended September 30, 2021 was £97.3 million or $131.1 million compared to £66.0 million for the same period in the prior year. The increases in operating loss were driven by increases in employee costs associated with a non-cash share-based payment charge.

Revenue for the three and nine months ended September 30, 2021 was £5.9 million or $8.0 million and £19.9 million or $26.8 million, respectively, as compared to £6.7 million and £22.7 million, respectively, for the three and nine months ended September 30, 2020. The decrease in revenue was primarily due to a reduction in activity under our collaboration agreements.

For the three and nine months ended September 30, 2021, our research and development ("R&D") expenses were £16.8 million or $22.6 million and £53.2 million or $71.6 million, respectively, as compared to £20.4 million and £57.6 million, respectively, for the three and nine months ended September 30, 2020. The reduction in R&D expenses was largely attributable to a reduction in clinical trial activity for tebentafusp as we seek regulatory approval and prepare for commercial launch.

For the three and nine months ended September 30, 2021, our administrative expenses were £20.0 million or $27.0 million and £64.0 million or $86.3 million, respectively, compared to £9.7 million and £31.6 million respectively, for the three and nine months ended September 30, 2020. The overall increase was driven by a £6.4 million and £19.3 million increase, respectively, in the non-cash share-based payment charge. In addition, pre-commercial expenditure relating to tebentafusp increased by £4.8 million and £10.4 million, respectively, in the three and nine months ended September 30, 2021.

Cash and cash equivalents were £256.6 million or approximately $345.6 million as of September 30, 2021 compared to £129.7 million as of December 31, 2020.

About Tebentafusp

Tebentafusp is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. Tebentafusp specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma, and is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect and activate T cells to recognise and kill tumour cells. Tebentafusp has been granted Priority Review; Real Time Oncology Review; Breakthrough Therapy Designation, Fast Track designation and orphan drug designation by the FDA in the United States; orphan drug status in the European Union; and Promising Innovative Medicine (PIM) designation under the UK Early Access to Medicines Scheme for metastatic uveal melanoma. The European Medicine Agency (EMA) has granted the tebentafusp Marketing Authorization Application (MAA) for an Accelerated Assessment procedure based on the Committee for Medicinal Products for Human Use (CHMP) agreement that tebentafusp is a product of major interest for public health and therapeutic innovation. Tebentafusp is also being reviewed under the FDA’s Project Orbis initiative, which enables concurrent review by the health authorities in partner countries that have requested participation. For more information about enrolling in tebentafusp clinical trials for metastatic uveal melanoma, please visit ClinicalTrials.gov (NCT03070392).