On November 9, 2022 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688), a patient-focused, innovative, commercial-stage, global biopharmaceutical company, reported financial results for the third quarter of 2022, along with recent product highlights and corporate updates (Press release, Zai Laboratory, NOV 9, 2022, View Source [SID1234623555]).

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!

"Zai Lab’s third quarter was marked by a new regional and highly synergistic collaboration, strong revenue growth across our commercial products, and significant progress toward achieving our remaining 2022 corporate priorities," said Dr. Samantha Du, Founder, Chairperson and CEO, of Zai Lab. "The company’s strategic positioning with respect to its targeted disease areas provides a robust and synergistic platform to benefit patients in Greater China and around the world as we continue to increase our sales and developmental efforts. Looking ahead, we expect this momentum to be bolstered by our late-stage development candidates that are progressing through pivotal studies and regulatory submissions. As one example, we reached an agreement with the NMPA on the development plan for a bridging study for KarXT in schizophrenia in China. In addition, our recently announced strategic collaboration with Seagen for the license of TIVDAK strengthens our ability to address unmet medical needs in women’s cancer. TIVDAK is the first and only ADC approved in the U.S. for the treatment of adult patients with recurrent or metastatic cervical cancer. Zai Lab is progressing this asset in pivotal studies in China."

Recent Product Developments and Anticipated Milestones

Oncology

ZEJULA (Niraparib)

ZEJULA is an oral, once-daily small-molecule poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor. It is the only PARP inhibitor approved in the United States, the European Union, and China as a first-line maintenance monotherapy for patients with advanced ovarian cancer, regardless of their biomarker status.

Recent Product Highlights

•Throughout this year, the U.S. Food and Drug Administration (FDA) has been reviewing data on PARP inhibitors, and other companies have issued Dear HCP Letters in the U.S. as a result of ongoing discussions with the FDA. In September 2022, Zai Lab partner GlaxoSmithKline (GSK) disclosed that it was in discussions with the FDA to discuss overall survival (OS) data from GSK’s ENGOT-OV16/NOVA phase III clinical trial for adult patients with recurrent ovarian cancer irrespective of the gBRCA mutation. Zai Lab does not expect the FDA’s discussions with GSK to impact its approval from the NMPA for ZEJULA in China. The NMPA’s full approval of ZEJULA in the recurrent ovarian cancer setting is based on a separate study, the NORA study, which is a Phase 3 randomized, double-blind, placebo-controlled study of ZEJULA that the Company independently conducted in China. While the NORA study is not fully mature, to date, favorable trends have been observed in OS irrespective of gBRCA mutation status. We expect to present this data at a future scientific congress. As a result, the Company does not anticipate that its second-line all-comer label in China will be affected by the FDA’s discussions with GSK. The Company also does not expect a change in its first-line label for ZEJULA; the FDA’s discussions with GSK do not apply to this indication.

1

Tumor Treating Fields

Tumor Treating Fields (TTFields) are electric fields that disrupt cancer cell division. Optune and Optune Lua, commercial TTFields devices, are approved or marketed in certain countries or regions for the treatment of newly diagnosed and recurrent glioblastoma and malignant pleural mesothelioma.

Recent Product Highlight

•As of September 30, 2022, Optune has been listed in 72 regional customized commercial health insurance plans guided by provincial or municipal governments (or supplemental insurance plans) since its commercial launch in China in the third quarter of 2020, compared to 25 supplemental insurance plans as of September 30, 2021.

Anticipated 2022 / Early 2023 Partner and Zai Milestones

•Last patient enrollment anticipated in the Phase 3 pivotal METIS study evaluating the efficacy and safety of stereotactic radiosurgery plus TTFields compared to stereotactic radiosurgery alone in patients with brain metastases resulting from Non-small Cell Lung Cancer (NSCLC).

•Top-line results from the Phase 3 pivotal LUNAR study in NSCLC in the early first quarter of 2023. Zai Lab joined the global LUNAR study in April 2021.

QINLOCK (Ripretinib)

QINLOCK is a switch-control tyrosine kinase inhibitor engineered to broadly inhibit KIT- and PDGFRα-mutated kinases. It is the only therapeutic approved in the United States and China for advanced gastrointestinal stromal tumor (GIST) patients who have received prior treatment with three or more kinase inhibitors in the all-comer setting.

Recent Product Highlights

•As of September 30, 2022, QINLOCK has been listed in 96 supplemental insurance plans since its commercial launch in China in May 2021, compared to 28 supplemental insurance plans as of September 30, 2021.

•In August 2022, the recommendation level of QINLOCK for second-line treatments for advanced GIST patients was advanced from Level III to Level II (1A evidence) in the Chinese Society of Clinical Oncology (CSCO) Guidelines for Diagnosis and Treatment of GIST 2022.

Anticipated 2022 Zai Milestone

•Seek National Reimbursement Drug List (NRDL) inclusion for a fourth-line GIST indication.

Adagrasib

Adagrasib is a highly selective and potent oral small-molecule inhibitor of KRASG12C for treating KRASG12C-mutated NSCLC, colorectal cancer (CRC), pancreatic cancer, and other solid tumors.

Recent Product Highlights

•In September 2022, Zai Lab partner Mirati Therapeutics, Inc. (Mirati) presented results from KRYSTAL-1, a multicohort Phase 1/2 study evaluating adagrasib with or without cetuximab in patients with advanced CRC harboring a KRASG12C mutation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022.
–Of the evaluable patients in the adagrasib monotherapy cohort (n=43), the investigator assessed confirmed objective response rate (ORR) was 19% (8/43) and the disease control rate (DCR) was 86% (37/43). The median duration of response (DOR) was 4.3 months (95% CI, 2.3–8.3) and median PFS was 5.6 months (95% CI, 4.1–8.3).
–Of the evaluable patients in the adagrasib plus cetuximab combination cohort (n=28), the investigator assessed confirmed ORR was 46% (13/28) and the DCR was 100% (28/28). The median DOR was 7.6 months (95% CI 5.7–NE) and median PFS was 6.9 months (95% CI, 5.4–8.1).
–The prognosis for patients with CRC has historically been poor in later lines of therapy with response rates of approximately 1-2% and median PFS of approximately 2 months in patients with late-line CRC; patients with KRASG12C-mutated CRC tend to have even worse outcomes than the broader CRC patient population.
2

–In the overall subset of patients with KRASG12C-mutated CRC evaluated in this study, adagrasib was found to be well-tolerated as a monotherapy and in combination with cetuximab. The majority of observed treatment-related adverse events (TRAEs) were grade 1-2 (59%); no grade 5 TRAEs were observed.

•In August 2022, Zai Lab treated the first patient in Greater China for the global Phase 2 KRYSTAL-7 study of adagrasib in combination with pembrolizumab in first-line KRASG12C-mutated NSCLC patients.

Anticipated 2022 Partner Milestones

•Potential FDA approval and commercial launch in the United States for adagrasib as the treatment for patients with NSCLC harboring the KRASG12C mutation who have received at least one prior systemic therapy; Prescription Drug User Free Act (PDUFA) target action date of December 14, 2022.

•Update for the Phase 2 KRYSTAL-7 study of adagrasib in combination with pembrolizumab in first-line KRASG12C-mutated NSCLC in the fourth quarter of 2022.

•Additional clarity on the regulatory pathway of adagrasib monotherapy in first-line KRASG12C-mutated NSCLC.

Bemarituzumab

Bemarituzumab is a potential first-in-class antibody that is being developed in gastric and gastroesophageal junction (GEJ) cancer as a targeted therapy for tumors that overexpress FGFR2b.

Recent Product Highlight

•Zai Lab partner Amgen continues to enroll patients in several studies of bemarituzumab, including:
–FORTITUDE-101, a Phase 3 study of bemarituzumab plus chemotherapy, versus placebo plus chemotherapy in first-line gastric cancer with FGFR2b overexpression.
–FORTITUDE-102, the Phase 3 portion of the 1b/3 study of bemarituzumab plus chemotherapy and nivolumab versus chemotherapy and nivolumab in first-line gastric cancer with FGFR2b overexpression.

Anticipated 2022 / Early 2023 Zai Milestone

•Initiate a registrational study of bemarituzumab in first-line advanced gastric and GEJ cancer in Greater China.

Odronextamab

Odronextamab is a bispecific antibody designed to trigger tumor killing by linking and activating a cytotoxic T-cell (binding to CD3) to a lymphoma cell (binding to CD20).

Anticipated 2022 Zai Milestone

•Complete enrollment in China in a potentially pivotal Phase 2 study in B-Cell Non-Hodgkin Lymphoma (B-NHL).

Anticipated 2022 Partner Milestone

•Report additional results from the potentially pivotal Phase 2 study in B-NHL.

Repotrectinib

Repotrectinib is a next-generation tyrosine kinase inhibitor (TKI) designed to effectively target ROS1 and TRK A/B/C, with the potential to treat TKI-naïve or TKI-pretreated patients.

Recent Product Highlights

•In October 2022, Zai Lab partner Turning Point Therapeutics (a wholly owned subsidiary of Bristol Myers Squibb Company) provided a clinical data update from the global, registrational Phase 1/2 TRIDENT-1 study of repotrectinib at the 34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium 2022.
–Repotrectinib continued to demonstrate meaningful clinical activity in patients with ROS1+ advanced NSCLC, who were TKI-naïve or TKI-pretreated, including with ROS1 G2032R resistance mutation. Durable responses and intracranial efficacy were observed in both TKI-naïve and TKI-pretreated patients.
3

–Repotrectinib also continued to show clinical activity in patients with NTRK+ advanced solid tumors who were TKI-naïve or TKI-pretreated, and responses were seen across diverse tumor types.
–Safety is well characterized, manageable with known protocols, and signals potential compatibility with long-term use.

•In October 2022, Zai Lab completed enrollment in China in all cohorts of the registrational Phase 1/2 TRIDENT-1 study.

Anticipated Early 2023 Zai Milestone

•Discuss regulatory pathway with the National Medical Products Administration (NMPA) at a pre-NDA meeting.

CLN-081

CLN-081 is an orally available, irreversible epidermal growth factor receptor (EGFR) inhibitor that selectively targets cells expressing EGFR exon 20 insertion mutations while sparing cells expressing wild type EGFR.

Anticipated 2022 Partner Milestone

•Initiate a pivotal study following the completion of a pharmacokinetic (PK) food effect study.

BLU-945

BLU-945 is a selective and potent investigational inhibitor of the activating EGFR L858R mutation and on-target T790M and C797S resistance mutations, for the potential treatment of EGFR-driven NSCLC.

Recent Product Highlight

•In November 2022, Zai Lab partner Blueprint Medicines presented an update on the Phase 1/2 SYMPHONY trial data supporting plans to develop BLU-945 in combination with osimertinib in first-line EGFR L858R mutation-positive NSCLC.

Autoimmune Disorders

VYVGART (Efgartigimod)

Efgartigimod is an antibody fragment designed to reduce disease-causing immunoglobulin G (IgG) autoantibodies and block the IgG recycling process. It binds to the neonatal Fc receptor (FcRn), which is widely expressed throughout the body and plays a central role in rescuing IgG from degradation.

Recent Product Highlights

•As of November 1, 2022, VYVGART (efgartigimod alfa-fcab) has been listed in 10 supplemental insurance plans in China.

•In September 2022, Zai Lab partner argenx announced the submission of a BLA to the FDA for subcutaneous (SC) efgartigimod for the treatment of generalized myasthenia gravis (gMG) in adult patients.

•In September 2022, argenx also announced that the European Commission (EC) has granted marketing authorization for VYVGART as an add-on to standard therapy for the treatment of adult patients with gMG who are anti-acetylcholine receptor (AChR) antibody positive.

Anticipated 2022 / Early 2023 Zai Milestones

•Launch the proof-of-concept trials in two autoimmune renal diseases.

•Continue to explore and advance additional indications in coordination with argenx.

Anticipated Early 2023 Partner Milestone

•Report topline data from the registrational ADHERE trial of SC efgartigimod for chronic inflammatory demyelinating polyneuropathy (CIDP) in the first quarter of 2023.

4

Infectious Disease

NUZYRA (Omadacycline)

NUZYRA is a once-daily oral and intravenous antibiotic for the treatment of adults with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). Zai Lab led the China development and obtained approval by the NMPA in December 2021.

Anticipated 2022 Zai Milestone

•Seek NRDL inclusion for CABP and ABSSSI indications.

Sulbactam-Durlobactam (SUL-DUR, Asia Pacific Rights)

Sulbactam-Durlobactam is a beta-lactam/beta-lactamase inhibitor combination that provides unique activity against Acinetobacter organisms, including carbapenem-resistant strains.

Anticipated 2022 / Early 2023 Zai Milestone

•Submit an NDA to the NMPA.

Neuroscience

KarXT

KarXT combines xanomeline, a novel muscarinic agonist, with trospium, an approved muscarinic antagonist. In November 2021, Zai partnered with Karuna Therapeutics, Inc. (Karuna) to develop KarXT in Greater China for the treatment of schizophrenia and possibly other indications like dementia-related psychosis.

Recent Product Highlights

•In September, 2022, Zai Lab obtained agreement from the NMPA on the development plan of a bridging study in schizophrenia in China.

•In October 2022, Zai Lab partner Karuna announced that data from the Phase 3 EMERGENT-2 trial of KarXT in schizophrenia was shared at the 35th European College of Neuropsychopharmacology (ECNP) Congress in Vienna, Austria. A poster presentation and symposium included previously reported efficacy and safety data, as well as new additional safety data from the trial.

•Karuna initiated the Phase 3 ADEPT-1 study evaluating KarXT as a treatment for psychosis in Alzheimer’s disease in the third quarter of 2022.

•Karuna completed enrollment in the Phase 3 EMERGENT-3 trial in schizophrenia in the fourth quarter of 2022.

Anticipated Early 2023 Partner Milestone

•Report topline data from the Phase 3 EMERGENT-3 trial in schizophrenia in the first quarter of 2023.

Global R&D Autoimmune Disorder Programs

ZL-1102 (IL-17 Human VH Antibody Fragment, Global Rights)

ZL-1102 is a novel human VH antibody fragment (Humabody) targeting the IL-17A cytokine with high affinity and avidity. Unlike other anti-IL-17 products, ZL-1102 is being developed as a topical treatment for mild-to-moderate chronic plaque psoriasis (CPP).

Recent Product Highlight

•In September 2022, Zai Lab presented results of the Phase 1 proof-of-concept study for ZL-1102 at the 2022 European Academy of Dermatology and Venereology Congress (EADV) in Milan, Italy.

5

Anticipated 2022 / Early 2023 Zai Milestone

•Initiate a global Phase 2 study for CPP.

Global R&D Oncology Programs

Recent Highlight

•In November 2022, Zai Lab presented data from its internal oncology pipeline at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Boston, Mass. These presentations focus on two key global discovery programs: ZL-1211, an anti-CLDN18.2 antibody, and ZL-1218, an anti-CCR8 antibody.

Corporate Updates

•In September 2022, Zai Lab entered into a collaboration and license agreement with Seagen, Inc. for the development and commercialization of TIVDAK in Greater China. TIVDAK is the first and only ADC approved in the U.S. for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy and is an important addition to our oncology portfolio.

•In the second half of 2022, Zai Lab has continued to enhance its global leadership team. For example, Dr. Peter Huang joined the Company from Zentalis Pharmaceutical in November as Chief Scientific Officer (CSO). Dr. Huang brings to the Company an extensive scientific background and strong leadership and research and development experience, including over 16 years working within the biopharmaceutical industry. Dr. Huang will be a key member of the Company’s executive management team and is responsible for leading and overseeing the Company’s discovery efforts and translational medicine. In addition, Alette Verbeek joined the Company from Novartis in October as SVP, Head of Global Strategic Partnering. She is our first employee based in Europe and is responsible, among other things, for leading our European business development efforts.

•In November 2022, The Stock Exchange of Hong Kong Limited ("Hong Kong Stock Exchange") approved the Company’s transition from a listing under Chapter 18A of the Listing Rules of the Hong Kong Stock Exchange (Biotech Companies) to a general listing under Rule 8.05(3) of the Listing Rules (Qualifications for Listing), as the Company has satisfied applicable revenue and market capitalization requirements for listing outside of Chapter 18A. As a result of this approval, the "B" marker will be removed from the Company’s stock short name on the Hong Kong Stock Exchange, effective November 11, 2022.

Third-Quarter 2022 Financial Results

•For the three months ended September 30, 2022, total revenues were $57.5 million, compared to $43.1 million for the same period in 2021. Net product revenues for the period were $39.2 million for ZEJULA, compared to $28.2 million for the same period in 2021; $10.7 million for Optune, compared to $10.7 million for the same period in 2021; $5.5 million for QINLOCK, compared to $4.3 million for the same period in 2021, and $1.5 million for NUZYRA, compared to nil for the same period in 2021.

•Research and Development (R&D) expenses were $99.5 million for the three months ended September 30, 2022, compared to $55.1 million for the same period in 2021. The increase in R&D expenses was primarily due to the $30.0 million upfront payment for the new collaboration and license agreement with Seagen in the third quarter of 2022, increased expenses related to ongoing and newly initiated clinical trials, and higher payroll and payroll-related expenses from increased R&D headcount and share-based compensation.

•Selling, General and Administrative (SG&A) expenses were $66.6 million for the three months ended September 30, 2022, compared to $59.0 million for the same period in 2021. The increase was primarily due to payroll and payroll-related expenses from increased commercial and general and administrative headcount and share-based compensation as Zai Lab continued to enhance infrastructure and commercial operations in anticipation of new drug approvals and launches. We expect our net product revenue to exceed cost of goods sold and commercial expenses in 2023.

•Net loss was $161.2 million for the three months ended September 30, 2022, compared to $96.4 million for the same period in 2021. The increase in net loss was primarily due to a $30.0 million upfront payment for the new collaboration and license agreement with Seagen and an increase in foreign exchange loss of $36.7 million, which is a non-cash adjustment. Net loss per ordinary share during the three months ended September 30, 2022 was $0.17, compared to $0.10 for the same period in 2021. Net loss per ADS during the three months ended September 30, 2022, was $1.68, compared to $1.01 for the same period in 2021.
6

•As of September 30, 2022, cash and cash equivalents, short-term investments, and restricted cash totaled $1,120.3 million, which we expect will provide us with cash runway through 2025.

Conference Call and Webcast Information

Zai Lab will host a live conference call and webcast tomorrow, November 10, 2022, at 8:00 a.m. ET. Listeners may access the live webcast by visiting the Company’s website at View Source Participants must register in advance of the conference call. Details are as follows:

Registration Link: https://register.vevent.com/register/BI98db73679f254c8eb1024c9df5ea85a8

All participants must use the link provided above to complete the online registration process in advance of the conference call. Upon registering, each participant will receive a dial-in number, Direct Event passcode, and a unique access PIN, which can be used to join the conference call.

A replay will be available shortly after the call and can be accessed by visiting the Company’s website at View Source

On November 9, 2022 Armata Pharmaceuticals, Inc. (NYSE American: ARMP) ("Armata" or the "Company"), a biotechnology company focused on pathogen-specific bacteriophage therapeutics for antibiotic-resistant and difficult-to-treat bacterial infections, reported financial results for its third quarter 2022 and provided a corporate update (Press release, AmpliPhi Biosciences, NOV 9, 2022, View Source [SID1234623554]).

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!

Third Quarter 2022 and Recent Developments:

·SWARM-P.a. enrolling final Phase 2 MAD cohort evaluating AP-PA02 in cystic fibrosis
·AP-PA02 Phase 2 non-cystic fibrosis bronchiectasis (NCFB) study progressing toward site activation and first patient dosed
·AP-SA02 bacteremia study progressing through Phase 1b cohort
·AP-SA02 prosthetic joint infection study advancing through start-up activities

"During the third quarter, we have made significant progress in the SWARM-P.a. study. We now anticipate enrolling the last subject in the fourth quarter with top-line data expected in early 2023," stated Dr. Brian Varnum, Chief Executive Officer of Armata. "Concurrently, we made progress with our second lead program, AP-SA02 in Staphylococcus aureus bacteremia, enrolling in the Phase 1b portion of the diSArm study while continuing to expand the study reach in the United States and abroad. Importantly, we achieved regulatory approvals required to activate clinical sites in Australia, which we believe may accelerate enrollment in this difficult-to-treat patient population. Finally, our pipeline expansion activities continue to progress, with ongoing site activation for the Tailwind study evaluating AP-PA02 in non-cystic fibrosis bronchiectasis, and study start-up activities for AP-SA02 in prosthetic joint infections."

Third Quarter 2022 Financial Results

Grant Revenue. The Company recognized grant revenue of approximately $1.3 million for the three months ended September 30, 2022, which represents Medical Technology Enterprise Consortium ("MTEC")’s share of the costs incurred for the Company’s AP-SA02 program for the treatment of Staphylococcus aureus bacteremia. The Company expects to receive $16.3 million in grant funding from MTEC administered by the U.S. Department of Defense and the Defense Health Agency and Joint Warfighter Medical Research Program. The Company recognized approximately $1.3 million of revenue in the comparable period in 2021.

Research and Development. Research and development expenses for the three months ended September 30, 2022, were approximately $8.4 million as compared to approximately $5.6 million for the comparable period in 2021. The company continues to invest in clinical trial and personnel related expenses associated with its primary development programs.

General and Administrative. General and administrative expenses for the three months ended September 30, 2022, were approximately $1.6 million as compared to approximately $1.8 million for the comparable period in 2021.

Loss from Operations. Loss from operations for the three months ended September 30, 2022, was $(8.6) million as compared to a loss from operations of approximately $(6.1) million for the comparable period in 2021.

Cash and Equivalents. As of September 30, 2022, Armata held approximately $25.4 million of unrestricted cash and cash equivalents, as compared to $10.3 million as of December 31, 2021.

As of November 4, 2022, there were approximately 36.1 million shares of common stock outstanding.

On November 9, 2022 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, reported financial results for the fiscal quarter ended September 30, 2022, and provided business updates (Press release, Erasca, NOV 9, 2022, View Source [SID1234623553]).

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!

"This quarter, we continued to advance our RAS/MAPK pathway-focused pipeline. In September, we reported promising preliminary Phase 1/1b data at our R&D Day for our two lead compounds, ERK1/2 inhibitor ERAS-007 and SHP2 inhibitor ERAS-601, in advanced solid tumors. Their monotherapy efficacy combined with favorable safety, tolerability, and pharmacokinetic data support their combination development. In July, we signed a second clinical trial collaboration and supply agreement (CTCSA) with Eli Lilly to explore the anti-EGFR antibody cetuximab with ERAS-601 for the treatment of triple wildtype (KRAS/NRAS/BRAF wildtype) metastatic colorectal cancer (CRC) and human papillomavirus (HPV)-negative advanced head and neck squamous cell carcinoma (HNSCC), followed last month by a second CTCSA with Pfizer to explore the CDK4/6 inhibitor palbociclib with ERAS-007 for the treatment of patients with KRAS- or NRAS-mutant CRC and KRAS-mutant pancreatic ductal adenocarcinoma (PDAC)," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "We were also pleased to share four poster presentations at last month’s 34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on ERAS-007, ERAS-601, our central nervous system (CNS)-penetrant EGFR inhibitor ERAS-801, and our KRAS G12D inhibitor program ERAS-4."

Dr. Lim continued, "Before year-end, we expect to file an IND for our CNS-penetrant KRAS G12C inhibitor ERAS-3490 in KRAS G12C mutant non-small cell lung cancer (NSCLC). In the first half of 2023, we anticipate initiating a dose escalation trial for ERAS-007 in combination with ERAS-601 and expect to report combination data for ERAS-007 in gastrointestinal malignancies and ERAS-601 in triple wildtype CRC. Our balance sheet remains strong, we continue to strategically advance our pipeline, and we remain on track to execute across our near-term catalysts."

Research and Development (R&D) Highlights

Presented Promising Phase 1/1b Data for ERAS-007 and ERAS-601: In September 2022, Erasca hosted a virtual R&D Day with key opinion leader David S. Hong, M.D., professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, presenting promising preliminary Phase 1/1b monotherapy data for ERK1/2 inhibitor ERAS-007 and SHP2 inhibitor
ERAS-601 in RAS/MAPK-altered solid tumors, including a subset of BRAF-driven solid tumors and highlighting future directions for ERAS-007 and ERAS-601 in advanced solid tumors. Twenty-three percent (6/26) of patients with RAS/MAPK-altered non-CRC solid tumors and 44% (4/9) with BRAF-driven non-CRC solid tumors responded (confirmed and unconfirmed partial responses) to single agent ERAS-007 or ERAS-601*

Four Poster Presentations at ENA Symposium: In October 2022, Erasca presented four poster presentations supporting the continued clinical development of ERK1/2 inhibitor ERAS-007, SHP2 inhibitor ERAS-601, CNS-penetrant EGFR inhibitor ERAS-801, and KRAS G12D inhibitor program ERAS-4

* Data cutoff dates of 11/6/20, 7/11/22, and 5/16/22 for ASN007-101, FLAGSHP-1, and HERKULES-1 trials, respectively.

Corporate Highlights

Expanded Geographical Footprint: In July 2022, Erasca opened its new location in South San Francisco, CA, to accommodate and unify its Northern California employee base

Entered into a CTCSA with Eli Lilly (Lilly): In July 2022, Erasca announced that it had entered into a CTCSA under which Lilly will supply its anti-EGFR inhibitor cetuximab (ERBITUX) at no cost in connection with a clinical proof-of-concept trial evaluating ERAS-601, Erasca’s oral SHP2 inhibitor, in various combinations, including with cetuximab for the treatment of triple wildtype (KRAS/NRAS/BRAF wildtype) metastatic CRC and HPV-negative advanced HNSCC as part of the ongoing Phase 1/1b FLAGSHP-1 trial. This CTCSA complements the CTCSAs Erasca previously entered into with Lilly and Pfizer, respectively, to evaluate cetuximab and encorafenib (BRAFTOVI) in combination with the ERK1/2 inhibitor ERAS-007 in the HERKULES-3 Phase 1b/2 trial

Entered a Strategic R&D Collaboration with MD Anderson: In August 2022, Erasca announced a strategic R&D collaboration with MD Anderson to evaluate multiple agents from Erasca’s pipeline targeting the RAS/MAPK pathway as either single-agent or combination therapies

Entered into a CTCSA with Pfizer: In October 2022, Erasca announced that it had entered into a CTCSA under which Pfizer will supply its CDK4/6 inhibitor palbociclib (IBRANCE) at no cost in connection with a clinical proof-of-concept trial evaluating ERAS-007 in combination with palbociclib for the treatment of patients with KRAS- or NRAS-mutant CRC and KRAS-mutant PDAC as part of the ongoing Phase 1b/2 HERKULES-3 trial in patients with gastrointestinal (GI) malignancies

Key Upcoming Milestones

ERAS-3490: CNS-penetrant KRAS G12C inhibitor

IND filing anticipated in the second half of 2022

HERKULES-1: Phase 1b/2 trial for ERAS-007/MAPKlamp in patients with advanced solid tumors

Initiation of a Phase 1b dose escalation trial for ERAS-007 in combination with ERAS-601 (Erasca’s first MAPKlamp approach) anticipated in the first half of 2023

HERKULES-3: Phase 1b/2 trial for ERAS-007 in patients with GI malignancies

Initial Phase 1b combination data anticipated in the first half of 2023

FLAGSHP-1: Phase 1/1b trial for ERAS-601 in patients with advanced solid tumors

Initial Phase 1b combination data in triple wildtype (KRAS/NRAS/BRAF wildtype) CRC anticipated in the first half of 2023

HERKULES-2: Phase 1b/2 trial for ERAS-007 in patients with advanced NSCLC

Initial Phase 1b combination data anticipated in 2023

Third Quarter 2022 Financial Results

Cash Position: Cash, cash equivalents, and marketable securities were $365.5 million as of September 30, 2022, compared to $459.2 million as of December 31, 2021. Erasca expects its current cash, cash equivalents, and marketable securities balance to fund operations into the second half of 2024.

Research and Development (R&D) Expenses: R&D expenses were $28.2 million for the quarter ended September 30, 2022, compared to $20.0 million for the quarter ended September 30, 2021. The increase was primarily driven by expenses incurred in connection with clinical trials, preclinical studies, discovery activities, facilities-related expenses and depreciation, stock-based compensation, and outsourced services and consulting fees. The quarter ended September 30, 2021 also included $1.7 million of in-process R&D expenses related to the cash payment of $1.7 million to The Regents of the University of California, San Francisco following the completion of Erasca’s IPO.

General and Administrative (G&A) Expenses: G&A expenses were $8.8 million for the quarter ended September 30, 2022, compared to $6.9 million for the quarter ended September 30, 2021. The increase was primarily driven by stock-based compensation, legal and accounting fees, and facilities and office-related expenses. The quarter ended September 30, 2021 also included recognition of $17.5 million of expenses related to the issuance of common stock as a contribution to the Erasca Foundation in conjunction with Erasca’s IPO.

Net Loss: Net loss was $35.5 million, or $(0.29) per basic and diluted share, for the quarter ended September 30, 2022, compared to $46.1 million, inclusive of the $17.5 million in expenses recorded for the common stock issued to the Erasca Foundation, or $(0.46) per basic and diluted share, for the quarter ended September 30, 2021.

On November 9, 2022 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported financial results for the third quarter of 2022, and raised the mid-point of 2022 total revenue guidance (Press release, Jazz Pharmaceuticals, NOV 9, 2022, View Source [SID1234623552]).

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!

"Our execution across our business continues to chart a clear path to delivering on Vision 2025. We have further strengthened our operations, and our business is performing well as we’ve diversified our revenue streams and rapidly deleveraged, while delivering meaningful top- and bottom-line growth. We have also achieved another important milestone — exiting October 2022, there are now more narcolepsy patients taking Xywav than Xyrem," said Bruce Cozadd, chairman and CEO of Jazz Pharmaceuticals. "We’re pleased with the performance across our key products: compelling Xywav adoption across both narcolepsy and idiopathic hypersomnia (IH) continues to drive oxybate durability, Epidiolex delivered significant year-over-year growth driven by underlying demand, strong demand for Rylaze underscores the substantial unmet need and Zepzelca remains the treatment of choice in second-line small cell lung cancer (SCLC). Based on this performance, we are raising the mid-point for our 2022 full year revenue guidance and continue to focus on long-term sustainable growth."

"We have prioritized and invested in key programs leading to significant progress across our pipeline. I’m pleased to announce we have enrolled the first patients in both our Phase 1 clinical trial of JZP815, a pan-RAF inhibitor, and our Phase 3 trial of Epidyolex in Japan," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "Upon close of the transaction, we are excited to further expand our pipeline with zanidatamab, a novel HER2-targeted bispecific antibody in late-stage trials with the potential to transform the current standard of care in multiple HER2-expressing cancers, and also through the initiation of a Phase 2 clinical trial evaluating suvecaltamide (JZP385) in Parkinson’s disease tremor. We also continue to advance the JZP441 orexin-2 receptor agonist program. Together, this pipeline progress underscores an exciting time for R&D at Jazz as we look to deliver innovative therapies for patients in critical need."

Key Highlights

Business and Execution

Compelling adoption of Xywav in narcolepsy and IH driving oxybate durability.
Achieved a significant milestone exiting October 2022, with more narcolepsy patients taking Xywav than Xyrem.
Expect Epidyolex to be launched in all five key European markets by year end, following recent successful completion of pricing and reimbursement in France.
Expanded oncology portfolio with zanidatamab, a novel, late-stage asset, currently being studied in two pivotal trials: first-line HER2-positive gastroesophageal adenocarcinoma (GEA) and second-line HER-2 positive biliary tract cancer (BTC)1.
Enrolled the first patient in a Phase 1 clinical trial evaluating JZP815 in patients with advanced or metastatic solid tumors with MAPK pathway alterations.
Enrolled the first patient in a Phase 3 pivotal trial of Epidyolex in Japan for Dravet Syndrome (DS), Lennox-Gastaut Syndrome (LGS) and Tuberous Sclerosis Complex (TSC).
Initiated a Phase 3 pivotal trial of Epidiolex for Epilepsy with Myoclonic-Atonic Seizures (EMAS), the fourth target indication for Epidiolex.
Initiated a Phase 2 trial for suvecaltamide (JZP385) in Parkinson’s disease tremor.
Financial

Raising the mid-point of 2022 total revenue guidance to $3.65 billion driven by increases in the guidance mid-point for both our Neuroscience and Oncology therapeutic areas.
Growing and durable commercial franchises drove 3Q22 total revenues of $940.7 million; 12% increase compared to the same period in 2021.
Continued progress in demonstrating operational excellence and ability to leverage our selling, general and administrative (SG&A) expenses, with SG&A expense as a percentage of sales decreasing in 3Q22 and year-to-date, relative to the same periods in 2021.
Strong operating cash flow year-to-date of $930.0 million, with a cash balance of $899.4 million as of September 30, 2022, and net leverage ratio of 2.9×2.
_______________________

1.

Pending transaction close.

2.

On a pro forma non-GAAP adjusted basis. Non-GAAP net leverage ratio is a non-GAAP financial measure. For further information, see "Non-GAAP Financial Measures."

Business Updates

Key Commercial Products

Oxybate (Xywav and Xyrem):

Net product sales for the combined oxybate business increased 11% to $512.0 million in 3Q22 compared to the same period in 2021.
Average active oxybate patients on therapy was approximately 17,600 in 3Q22, an increase of approximately 10% compared to the same period in 2021.
Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution:

Xywav net product sales increased 67% to $255.9 million in 3Q22 compared to the same period in 2021.
There were approximately 9,500 active Xywav patients exiting 3Q22.
Xywav has broad patent protection to 2033.
Xywav for Narcolepsy:

There were approximately 8,050 narcolepsy patients taking Xywav exiting 3Q22.
Achieved another significant milestone exiting October 2022, with more narcolepsy patients taking Xywav than Xyrem.
The benefits of lowering sodium intake continue to resonate with patients and prescribers. In June 2021, the U.S. Food and Drug Administration (FDA) recognized seven years of Orphan Drug Exclusivity (ODE), through July 2027, for Xywav and published its summary of clinical superiority findings.
Xywav for Idiopathic Hypersomnia (IH):

Compelling growth with approximately 1,450 IH patients taking Xywav exiting 3Q22.
The Company has achieved its goal of obtaining similar payer coverage to narcolepsy, with coverage now at approximately 90% of commercial lives for IH.
The Company launched Xywav, the first and only treatment approved by FDA for IH, in November 2021. Initial launch efforts have focused on the approximately 37,000 currently diagnosed patients in the U.S. who are actively seeking healthcare. Healthcare providers are excited to have a treatment option with positive and compelling clinical trial results that addresses IH and not just its symptoms.
FDA recognized ODE for IH in January 2022, extending regulatory exclusivity to August 2028.
Xyrem (sodium oxybate) oral solution:

Xyrem net product sales decreased 17% to $256.0 million in 3Q22 compared to the same period in 2021, reflecting the continued adoption of Xywav by patients with narcolepsy.
Epidiolex/Epidyolex (cannabidiol):

Epidiolex/Epidyolex net product sales increased 22% to $196.2 million in 3Q22 compared to the same period in 2021.
The Company successfully completed the pricing and reimbursement process for Epidyolex in France and expects commercial launch by the end of 2022, which would make Epidyolex commercially available and reimbursed in all five key European markets: United Kingdom, Germany, Italy, Spain and France.
The Company enrolled the first patient in a pivotal Phase 3 trial of Epidyolex for DS, LGS and TSC in Japan.
The Company initiated a Phase 3 pivotal trial of Epidiolex for EMAS, the fourth target indication for Epidiolex.
Zepzelca (lurbinectedin):

Zepzelca net product sales decreased 2% to $70.3 million in 3Q22 compared to the same period in 2021. As previously noted, 3Q21 net product sales were favorably impacted by approximately $10 million, relating to a reduction in the returns accrual rate, due to lower than estimated actual returns. Excluding this impact, net product sales increased by approximately 14% in 3Q22 compared to the same period in 2021.
The Company is pleased Zepzelca continues to be the treatment of choice in the second-line SCLC setting, a position established after only eighteen months on the market.
Zepzelca development program highlights:
The EMERGE-201 Phase 2 basket trial evaluating Zepzelca as monotherapy in select relapsed/refractory solid tumors is ongoing.
Phase 3 trial in partnership with F. Hoffmann-La Roche Ltd (Roche) to evaluate first-line use of Zepzelca in combination with Tecentriq (atezolizumab), compared to Tecentriq alone, as maintenance therapy in patients with extensive-stage SCLC after induction chemotherapy is ongoing.
The Company’s partner, PharmaMar, is conducting the Phase 3 confirmatory trial, LAGOON, in second-line SCLC. If positive, this trial could confirm the benefit of Zepzelca in the treatment of SCLC when patients progress following first-line treatment with a platinum-based regimen.
Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn):

Rylaze net product sales were $73.5 million in 3Q22.
The continued strong launch of Rylaze reflects the significant unmet patient need for a high-quality, reliable supply of Erwinia asparaginase for patients with acute lymphoblastic leukemia.
In May 2022, the Company completed the Marketing Authorization Application (MAA) submission to European Medicines Agency (EMA) for a Monday/Wednesday/Friday (MWF) dosing schedule and intramuscular (IM) and intravenous (IV) administration for JZP458 (approved as Rylaze in the U.S.) with potential for approval in 2023. The Company is also advancing the program for potential submission, approval and launch in Japan.
In January 2022, the Company completed the submission of a supplemental Biologics Licensing Application (sBLA) to FDA seeking approval for a MWF IM dosing schedule for Rylaze. In April 2022, the Company completed the submission of an sBLA to FDA seeking approval for IV administration of Rylaze. Both submissions are being reviewed under the Real-time Oncology Review Program (RTOR).
Corporate Development

Zanidatamab Agreement1:

On October 19, 2022, the Company and Zymeworks Inc. announced an exclusive licensing agreement under which Jazz will acquire development and commercialization rights to zanidatamab, a novel HER2-targeted bispecific antibody, which can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding.
The Company believes zanidatamab has the potential to deliver significant long-term value and meaningfully contribute to Vision 2025.
The late-stage program for zanidatamab is aligned strategically with Jazz’s focus on opportunities where there is significant unmet patient need, and where we can apply our unique insights and leverage existing integrated capabilities and global infrastructure to commercialize efficiently.
Zanidatamab has multiple novel mechanisms of action applicable in several HER2-positive tumors where it has demonstrated compelling anti-tumor activity, both as a monotherapy and in combination with chemotherapy.
Top-line clinical data for zanidatamab in BTC (HERIZON-BTC-01) is expected by the end of 2022 and has the potential to support global regulatory filings.
Zymeworks is eligible to receive a $50 million upfront payment, following the clearance relating to the U.S. Hart-Scott Rodino Antitrust Improvements Act of 1976, or HSR Clearance. Should Jazz decide to continue the collaboration following readout of the top-line clinical data from HERIZON-BTC-01, Zymeworks is eligible to receive a second payment of $325 million.
_______________________

1.

Subject to closing conditions, Jazz to obtain exclusive development and commercialization rights to zanidatamab across all indications in the United States, Europe, Japan and all other territories except for those Asia/Pacific territories previously licensed by Zymeworks.

Key Pipeline Highlights

Nabiximols:

On June 28, 2022, the Company announced the Phase 3 RELEASE MSS1 trial (NCT04657666) in multiple sclerosis (MS)-related spasticity did not meet the primary endpoint of change in Lower Limb Muscle Tone-6 (LLMT-6) between baseline and Day 21, as measured by the Modified Ashworth Scale (MAS).
The analysis of the nabiximols MSS1 trial has been completed. The Company has assessed the nabiximols program’s potential to support regulatory approval in the U.S., as well as in the context of its broader pipeline opportunities, and has made the decision to discontinue the program.
Sativex (nabiximols) was approved outside the U.S. based on a comprehensive clinical trial program, including three positive Phase 3 randomized controlled trials completed in Europe. The Company continues to believe Sativex confers benefit to patients with MS-related spasticity and continues to support the availability of Sativex in the 29 markets outside the U.S., where it is approved.
RELEASE MSS1 trial results will be presented at a future medical meeting.
The Company remains committed to the GW Cannabinoid Platform and is working to advance multiple early-stage cannabinoid programs with the potential to address critical unmet patient needs.
Suvecaltamide (JZP385):

Suvecaltamide, a highly selective modulator of T-type calcium channels, is in clinical development for the treatment of essential tremor (ET) and Parkinson’s disease tremor.
Patient enrollment is ongoing in the Phase 2b ET trial and top-line data read-out is anticipated in 1H24.
The Company initiated a Phase 2 trial in patients with Parkinson’s disease tremor and expects the first patient to be enrolled by year end.
JZP150:

JZP150, a selective fatty acid amide hydrolase, or FAAH, inhibitor, is in clinical development for the potential treatment of post-traumatic stress disorder (PTSD).
Patient enrollment is ongoing and top-line data read-out is anticipated in late 2023.
The Company received Fast Track Designation for JZP150 development in PTSD from FDA in 4Q21, underscoring the significant unmet medical needs of patients.
JZP815:

The Company enrolled the first patient in a Phase 1 trial evaluating JZP815 in patients with advanced or metastatic solid tumors with MAPK pathway alterations.
The pan-RAF inhibitor program is part of a novel class of next-generation precision oncology therapies that has the potential to benefit cancer patients with high unmet needs in multiple different solid tumors.
JZP441:

JZP441, a potent, highly selective oral orexin-2 receptor agonist designed to activate orexin signaling, is in clinical development in Japan in a Phase 1 trial to evaluate safety, tolerability and pharmacokinetics in healthy volunteers.
The Company continues to advance the JZP441 program.
GAAP net loss in 3Q22 was $(19.6) million, or $(0.31) per diluted share, compared to $(52.8) million, or $(0.86) per diluted share, for 3Q21. Non-GAAP adjusted net income in 3Q22 was $370.4 million, or $5.17 per diluted share, compared to $261.4 million, or $4.20 per diluted share, for 3Q21. Reconciliations of applicable GAAP reported to non-GAAP adjusted information are included at the end of this press release.

Total revenues increased 12% in 3Q22 compared to the same period in 2021.

Neuroscience net product sales in 3Q22 increased 10% to $711.4 million compared to the same period in 2021 primarily driven by oxybate net product sales which increased 11% to $512.0 million in 3Q22 compared to the same period in 2021 and Epidiolex/Epidyolex net product sales which increased 22% to $196.2 million compared to the same period in 2021.
Oncology net product sales in 3Q22 increased 21% to $223.4 million compared to the same period in 2021 primarily driven by Rylaze net product sales which increased to $73.5 million in 3Q22 compared to the same period in 2021 following product launch in July 2021.
Changes in operating expenses in 3Q22 over the prior year period are primarily due to the following:

Cost of product sales decreased in 3Q22 compared to the same period in 2021, on a GAAP basis, primarily due to a lower acquisition accounting inventory fair value step-up expense in 3Q22, compared to 3Q21 and, on a non-GAAP adjusted basis, primarily due to product mix.
SG&A expenses decreased in 3Q22 compared to the same period in 2021, on a GAAP basis, primarily due to lower GW acquisition related transaction and integration expenses, offset by restructuring costs and costs related to program terminations. SG&A expenses in 3Q22, on a GAAP and non-GAAP adjusted basis, included lower marketing related expenses compared to 3Q21.
Research and development (R&D) expenses increased in 3Q22 compared to the same period in 2021, on a GAAP basis, primarily due to restructuring costs. R&D expenses in 3Q22, on a GAAP and non-GAAP adjusted basis, included lower clinical program expenses related to JZP458 (Rylaze) and solriamfetol related programs compared to 3Q21.
The impairment charge in 3Q22, on a GAAP basis, related to an acquired IPR&D asset impairment relating to the discontinuation of our nabiximols program.
Cash Flow and Balance Sheet

As of September 30, 2022, cash, cash equivalents and investments were $899.4 million, and the outstanding principal balance of the Company’s long-term debt was $5.8 billion compared to $6.4 billion as of December 31, 2021. In addition, the Company had undrawn borrowing capacity under a revolving credit facility of $500 million. For the nine months ended September 30, 2022, the Company generated $930.0 million of cash from operations. In 3Q22 the Company made a voluntary payment of $300.0 million on the Dollar Term Loan and in 1Q22 the Company repaid in full the $251.0 million remaining aggregate principal amount of the Euro Term Loan B.

2022 Financial Guidance

The Company has raised the mid-point of 2022 total revenue guidance to $3.65 billion driven by increases in the guidance mid-point for both our Neuroscience and Oncology therapeutic areas.

Conference Call Details

Jazz Pharmaceuticals will host an investor conference call and live audio webcast today at 4:30 p.m. ET (9:30 p.m. GMT) to provide a business and financial update and discuss its 2022 third quarter results.

Interested parties may register for the call in advance here or via the Investors section of the Jazz Pharmaceuticals website at www.jazzpharmaceuticals.com. To ensure a timely connection, it is recommended that participants register at least 15 minutes prior to the scheduled webcast.

A replay of the webcast will be available via the Investors section of the Jazz Pharmaceuticals website at www.jazzpharmaceuticals.com.

On November 9, 2022 IO Biotech (Nasdaq: IOBT), a clinical-stage biopharmaceutical company developing novel, immune-modulating cancer therapies based on its T-win technology platform, reported financial results for the quarter ending September 30, 2022 (Press release, IO Biotech, NOV 9, 2022, View Source [SID1234623551]).

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!

"During the last three months, we have made significant progress with the activation of clinical sites participating in our global Phase 3 combination trial of IOB102-IO103 with pembrolizumab as a potential first-line treatment in advanced melanoma," said Mai-Britt Zocca, Ph.D., President and Chief Executive Officer of IO Biotech. "We ended October with 55 sites actively enrolling in study, compared to 19 actively enrolling sites at the end of July. We view the pace of site activation as a leading indicator of patient enrollment, and we are very pleased with our progress."

Dr. Zocca continued, "Additionally, enrollment in our second ongoing clinical study, the Phase 2 basket trial of IO102-IO103 in combination with pembrolizumab, is progressing nicely and we continue to expect to receive preliminary data in one indication this quarter with additional data in 2023. We believe that our T-win platform—and its novel approach to activate naturally occurring T cells to target immunosuppressive mechanisms—has the potential to benefit patients in need of more treatment options and look forward to reporting our progress in the coming months."

Highlights for Third Quarter 2022 and Recent Weeks

An oral presentation and two poster presentations related to the company’s programs are being presented at the 2022 SITC (Free SITC Whitepaper) Meeting this week. See the following press release for more information, "IO Biotech ApS—IO Biotech Announces Invited Oral Presentation and Two Poster Presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting."

Consistent with the earlier reported data, with an additional 12 months of patient follow-up, results from a new October 2022 data cut for the MM1636 Phase 1/2 study with IO102-IO103 in combination with nivolumab for metastatic melanoma continue to be encouraging. As of that data cut-off, 30 PD-1 naïve patients were enrolled with a median follow-up time of 31.7 months. Median overall survival (mOS) was reached at 46.8 months post first trial treatment, median progression free survival (mPFS) was 22.5 months, and 50% of patients (15/30) achieved a complete response (CR), or complete disappearance of their tumors. The overall response rate for the study was 73.3% as previously reported. Patients who were PD-1 refractory and enrolled in cohort B in this study had no response to therapy, which we believe shows that our vaccine works best in front-line metastatic melanoma patients, as we expected in this setting.

In the past three months, the company has accelerated the rate of clinical trial site activation in the global Phase 3 trial of IO102-IO103 in combination with pembrolizumab for front-line treatment of PD-1 naïve metastatic melanoma patients.

In October 2022, the company named Amy Sullivan as Chief Financial Officer. Ms. Sullivan brings 30 years of experience building biotech companies to IO Biotech.

In November 2022, the company entered into a fourth clinical trial collaboration and supply agreement with Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside the United States and Canada), through a subsidiary. See the following press release for more information, "IO Biotech ApS—IO Biotech Announces New Clinical Collaboration with Merck to Evaluate Neoadjuvant and Adjuvant IO102-IO103 in Combination With KEYTRUDA (pembrolizumab) in a Phase 2, Multi-cohort Trial in Patients with Resectable Tumors."

Third Quarter Financial Results

Net loss for the three months ended September 30, 2022 was $15.7 million, compared to $4.5 million for the three months ended September 30, 2021.

Research and development expenses were $10.0 million for the three months ended September 30, 2022, compared to $4.1 million for the three months ended September 30, 2021. The increase of $5.9 million was primarily related to an increase in preclinical studies and clinical trial-related activities for our IO102-IO103 product candidate, including the continued execution of our Phase 3 clinical trial, of $2.9 million and an increase in personnel costs of $2.8 million primarily related to an increase in headcount and related recruiting costs.

General and administrative expenses were $5.8 million for the three months ended September 30, 2022, compared to $2.9 million for the three months ended September 30, 2021. The increase of $2.9 million was primarily related to costs associated with being a public company.

Other income, net was $0.3 million for the three months ended September 30, 2022, compared to $2.6 million for the three months ended September 30, 2021. The decrease of $2.3 million was primarily due to the decrease in the fair value adjustments on the Company’s preferred stock tranche obligations.

Cash and cash equivalents as of September 30, 2022 were $151.2 million, compared to $211.5 million at December 31, 2021. During the third quarter 2022, the Company used cash, cash equivalents and restricted cash of $13.5 million from operating, investing and financing activities with an additional decrease of $5.5 million in cash due to the effects of foreign currency exchange rates. Cash on hand is expected to support operations through anticipated data readouts into mid-2024.

About the IOB-013/KN-D18 Clinical Trial

IOB-013/KN-D18 (Clinical Trials.gov: NCT05155254) is an open label, randomized Phase 3 clinical trial being conducted in collaboration with Merck of IO102-IO103 in combination with pembrolizumab versus pembrolizumab alone in patients with previously untreated, unresectable or metastatic (advanced) melanoma. Target enrollment will be 300 patients from centers spread across Europe, Australia, and the United States. Biomarker analyses will also be conducted. IO Biotech will sponsor the Phase 3 trial and Merck will supply pembrolizumab. IO Biotech maintains global commercial rights to IO102-IO103.

About IOB-022/KN-D38

IOB-022/KN-D38 is a non-comparative, open label Phase 2 trial to investigate the safety and efficacy of IO102-IO103 in combination with pembrolizumab in each of the following first-line indications: non-small cell lung cancer, squamous cell carcinoma of the head and neck, and metastatic urothelial bladder cancer. The clinical trial will be sponsored by IO Biotech and conducted in collaboration with Merck. IO Biotech maintains global commercial rights to IO102-IO103.

About IO102-IO103

IO102-IO103 is an investigational cancer immunotherapy designed to target the immunosuppressive mechanisms mediated by the key immunosuppressive proteins indoleamine 2,3-dioxygenase (IDO) and PD-L1.