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Lyell Immunopharma Receives FDA Orphan Drug Designation for LYL845 for the Treatment of Melanoma

On November 9, 2023 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical‑stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors, reported that the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to LYL845, an investigational tumor infiltrating lymphocyte (TIL) product candidate for the treatment of patients with stage IIB-IV melanoma (Press release, Lyell Immunopharma, NOV 9, 2023, View Source [SID1234637379]).

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"There remains a high unmet medical need for patients with advanced melanoma and we believe LYL845 has the potential for differentiated potency and durability needed to deliver better outcomes for patients with melanoma as well as other solid tumors where TIL therapy has not yet been widely effective," said Lynn Seely, M.D., Lyell’s President and CEO. "We are pleased to have received Orphan Drug Designation for LYL845 in advanced melanoma and look forward to presenting initial clinical data from this program next year."

LYL845, an autologous TIL product candidate enhanced with Lyell’s Epi-R manufacturing protocols, is currently being investigated in a Phase 1 clinical trial in patients with relapsed or refractory metastatic or locally advanced melanoma, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC). In nonclinical studies, LYL845 TIL expanded with Epi-R exhibit characteristics that have previously been associated with improved clinical response rate, including a higher percentage of cytotoxic T cells and stemness phenotypes. LYL845 TIL have also demonstrated enhanced T-cell potency and maintenance of tumor-reactive polyclonality in nonclinical experiments. Initial data from Lyell’s ongoing Phase 1 clinical trial are expected in 2024.

The FDA’s Orphan Drug Designation program provides orphan status to drugs or biologics intended for the prevention, diagnosis, or treatment of diseases that affect fewer than 200,000 people in the United States. Sponsors of medicines that are granted Orphan Drug Designation are entitled to certain incentives, including tax credits for qualified clinical trials, prescription drug user-fee exemptions, and potential seven-year marketing exclusivity upon FDA approval.

Phase 1 Trial Design (NCT05573035)

The Phase 1 clinical trial is an open-label, dose-escalation trial for patients with relapsed and/or refractory metastatic or locally advanced melanoma with expansion cohorts for patients with melanoma, NSCLC, and CRC. The primary objective of the trial is to determine safety, tolerability and a recommended phase 2 dose range of LYL845. The secondary objective is to determine antitumor activity as evaluated by response rates, duration of response, progression-free survival and overall survival. Exploratory biomarkers of T-cell stemness will also be assessed.

About Melanoma

Melanoma of the skin is among the most common cancers in the United States. It is one of the most common cancers in young adults and especially in young women. It is estimated there are over 100,000 new cases of melanoma diagnosed in the United States per year. Melanoma arises due to genetic mutations in melanocytes, the pigment producing cells, which can be found in the skin, eye, inner ear and leptomeninges, and represents the most aggressive and the deadliest form of skin cancer. Although melanoma accounts for only ~1% of all dermatologic cancers, it is responsible for ~80% of deaths from skin cancer, with only ~14% of patients with advanced melanoma surviving for five years.

About LYL845

LYL845 is an investigational autologous TIL product enhanced with Epi-R manufacturing protocols for patients with relapsed and/or refractory metastatic or locally advanced melanoma, NSCLC and CRC. In nonclinical studies, Epi-R creates polyclonal populations of T cells that demonstrate properties of durable stemness and anti-tumor functionality. Durable stemness is the ability of T cells to persist and self-renew to drive durable tumor cytotoxicity.

TIL products are created by expanding T cells taken from the patient’s own tumor. Previous clinical experiences suggest that the efficacy of adoptive transfer of ex vivo expanded TILs is largely driven by specific recognition of mutated tumor neoantigens specific to each patient. To date, broad efficacy of TIL therapies has been limited by variable and often poor product quality, lack of stemness or potential durability of expanded TILs, failure to maintain polyclonality of TILs during production, and failure to enrich the TIL product with tumor-reactive T cells. TIL products manufactured using Lyell’s Epi-R manufacturing protocol aim to overcome these challenges. Nonclinical studies supporting the development of LYL845 suggest Epi-R technology improves TIL products by maintaining properties of durable stemness, which leads to superior ex vivo cell expansion and product qualities, maintenance of tumor reactive clones, and enhanced polyclonality.

Lineage Cell Therapeutics Reports Third Quarter 2023 Financial Results and Provides Business Update

On November 9, 2023 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, reported financial and operating results for the third quarter ended September 30, 2023 and will host a conference call today at 4:30 p.m. Eastern Time to discuss these results and provide a business update (Press release, Lineage Cell Therapeutics, NOV 9, 2023, View Source [SID1234637378]).

"The Lineage team has continued to advance our clinical and preclinical pipeline of differentiated cell transplant programs, supporting our alliances and working to establish new collaborations," stated Brian M. Culley, Lineage CEO. "The most important area of attention for our team remains our partnership with Roche and Genentech and our support for the ongoing Phase 2a clinical study of OpRegen in patients with geographic atrophy secondary to AMD. Through presentations at medical and scientific conferences, we have broadened awareness of OpRegen’s potential to provide durable anatomical and functional improvements in patients with GA. Most recently, additional observations of rapid improvements to outer retinal structure in the initial Phase 1/2a clinical study of OpRegen were reported; improvements were detectable within the first three months following a single administration, suggesting that OpRegen RPE cells may provide support to the patients’ remaining retinal cells within atrophic areas. Looking forward, we are working with our partners, Roche, and Genentech, on additional clinical data updates on the OpRegen program."

"In addition, our team continued the necessary work to submit our Investigational New Drug amendment for OPC1 to enable us to initiate the DOSED clinical study in subacute and chronic spinal cord injury patients," Mr. Culley added. "In parallel, we also initiated certain development activities under our partnership with Eterna Therapeutics, reflecting a key step in a corporate strategy to capitalize on our existing process development capabilities by combining them with cutting-edge cell engineering and editing technologies, to create novel and potentially superior product profiles. As always, we intend to advance our business and programs in a responsible and fiscally conservative way, with an overarching focus on providing a meaningful impact for patients through the development of differentiated allogeneic cell transplants."

Recent milestones and activities included:

RG6501 (OpRegen)
Continued execution under our collaboration with Roche and Genentech across multiple functional areas, including support for the ongoing Phase 2a multi-center clinical study in patients with GA secondary to AMD. Additional sites expected to come online for the Phase 2a study.
Results of imaging analyses demonstrating rapid improvement in outer retinal structure from patients enrolled in the prior Phase 1/2a clinical study, were presented at the 23rd EURETINA Congress:
All five patients who had extensive coverage of the GA lesion with the surgical bleb containing OpRegen in suspension demonstrated evidence of improvement in outer retinal structure as assessed by optical coherence tomography (OCT) within the first three months after treatment.
Retinal structural improvements were initially observed on day 1 (n=1), day 14 (n=1), month 1 (n=2), and month 3 (n=1).
Structural improvement on OCT was qualitatively defined as meeting all pre-specified criteria on at least two non-adjacent B scans including: 1) reduction in outer plexiform layer (OPL) and/or inner nuclear layer (INL) subsidence; 2) reappearance of external limiting membrane (ELM); and 3) increased hyperreflectivity and/or thickness of RPE and/or Bruch’s membrane or reduction of hypertransmission on at least two non-adjacent B scans.
Structural improvement was only observed within GA lesions with extensive coverage with the surgical bleb, suggesting that OpRegen RPE cells provide support to the remaining retinal cells within atrophic areas.
These five patients had an average of 4.4 letter best corrected visual acuity (BCVA) gain by 3 months and 12.8 letter BCVA gain by 1 year compared to baseline.
U.S. Patent No.11,746,324 entitled "Large Scale Production of Retinal Pigment Epithelial Cells," issued.
Investigational New Drug (IND) amendment preparation for clinical testing of novel OPC1 spinal cord delivery system continues
Company remains on track to submit IND amendment to FDA in Q4 2023 to enable initiation of the DOSED clinical study in subacute and chronic spinal cord injury patients.
Initiated Development Activities for Hypoimmune Pluripotent Cell Line for Neurology Indications Under Partnership with Eterna Therapeutics
Lineage evaluated its development strategy with a group of leading neurology experts in the U.S. and abroad and following an assessment of the competitive landscape, finalized its selection of specific gene edits for the initial cell lines to be developed by Eterna.
The edits include: the targeted deletion of the B2M gene, designed to reduce the immunogenicity of product candidates derived from the lines by inhibiting rejection by CD8+ T cells; the targeted insertion of the HLA-E gene, designed to overexpress HLA-E and prevent the allogeneic NK cell response; and a third undisclosed edit intended to confer clinical differentiation and a competitive advantage in the applicable indications.
Positive ANP1 initial proof of concept results from collaboration with the University of Michigan
Initial results demonstrated delivery, engraftment, and survival of ANP1 cells into specific target areas.
Results support advancement of the ANP1 program into functional preclinical testing.
Balance Sheet Highlights

Cash, cash equivalents, and marketable securities totaled $41.3 million as of September 30, 2023, which is expected to support planned operations into Q1 2025.

Third Quarter Operating Results

Revenues: Lineage’s revenue is generated primarily from licensing fees, royalties, collaboration revenues, and research grants. Total revenues for the three months ended September 30, 2023 were $1.2 million, a net decrease of $1.8 million as compared to approximately $3.0 million for the same period in 2022. The decrease was primarily driven by lower collaboration and licensing revenue recognized from deferred revenues from the Collaboration and License Agreement among Lineage and Roche and Genentech entered into in December 2021.

Operating Expenses: Operating expenses are comprised of research and development ("R&D") expenses and general and administrative ("G&A") expenses. Total operating expenses for the three months ended September 30, 2023 were $7.8 million, a decrease of $0.2 million as compared to $8.0 million for the same period in 2022.

R&D Expenses: R&D expenses for the three months ended September 30, 2023 were $3.7 million, a net increase of $0.1 million as compared to $3.6 million for the same period in 2022. The net increase was primarily driven by $0.2 million in higher OPC1 program-related expenses, and $0.5 million in expenses to support preclinical and other research and development programs. These increases were partially offset by a $0.5 million decrease in our VAC program, primarily related to reduced manufacturing activities.

G&A Expenses: G&A expenses for the three months ended September 30, 2023 were $4.0 million, a net decrease of approximately $0.4 million as compared to $4.4 million for the same period in 2022. The decrease was primarily attributable to an overall reduction in costs incurred for services by third parties, consulting costs, and recruiting related expenses.

Loss from Operations: Loss from operations for the three months ended September 30, 2023 was $6.7 million, an increase of $1.5 million as compared to a loss of $5.2 million for the same period in 2022.

Other Income/(Expenses), Net: Other income (expenses), net for the three months ended September 30, 2023 reflected other expense, net of approximately ($0.4) million, compared to other expense, net of ($0.3) million for the same period in 2022. The net change was primarily driven by exchange rate fluctuations related to Lineage’s international subsidiaries and fair market value changes in marketable equity securities, partially offset by interest income from our marketable debt securities.

Net Loss Attributable to Lineage: The net loss attributable to Lineage for the three months ended September 30, 2023 was $7.1 million, or $0.04 per share (basic and diluted), compared to a net loss attributable to Lineage of $6.1 million, or $0.04 per share (basic and diluted), for the same period in 2022.

Conference Call and Webcast

Interested parties may access today’s conference call and webcast, by dialing (800) 715-9871 from the U.S. and Canada and should request the "Lineage Cell Therapeutics Call". A live webcast of the conference call will be available online in the Investors section of Lineage’s website. A replay of the webcast will be available on Lineage’s website for 30 days and a telephone replay will be available through November 16, 2023, by dialing (800) 770-2030 from the U.S. and Canada and entering conference ID number 2323932.

Kiromic BioPharma Announces Deltacel™ Phase 1 Clinical Trial Enters Patient Recruitment Phase at Beverly Hills Cancer Center

On November 9, 2023 Kiromic BioPharma, Inc. (OTC PINK: KRBP) ("Kiromic" or the "Company"), a clinical-stage, fully-integrated biotherapeutics company using its proprietary DIAMOND artificial intelligence and data mining platform to develop cell therapies with a focus on immuno-oncology, reported the Deltacel Phase 1 Clinical Trial is now recruiting patients at the Beverly Hills Cancer Center (BHCC) (Press release, Kiromic, NOV 9, 2023, View Source [SID1234637377]). The study will evaluate Deltacel (KB-GDT-01), Kiromic’s allogeneic, off-the-shelf, Gamma Delta T-cell (GDT) therapy, in patients with metastatic non-small cell lung cancer (NSCLC).

The Company continues to engage additional clinical trial sites across the U.S, and will provide updates as additional sites are activated, and as patient recruitment starts at those locations.

The Phase 1 trial, titled "Safety Study for a Gamma Delta T Cell Product Used With Low Dose Radiotherapy in Patients With Stage 4 Metastatic NSCLC" (ID# NCT06069570), expects to enroll up to 48 patients. In this open-label, two-part trial, patients with stage 4 NSCLC will receive two intravenous infusions of Deltacel along with four courses of low-dose, localized radiation, over a 10-day period. The primary objective of the study is to evaluate the safety of Deltacel in combination with low-dose radiation; the secondary outcome measures are objective response, progression-free survival, overall survival, time to progression, time to treatment response, and disease control rates.

"We are delighted to announce the start of patient recruitment in our first clinical trial, and we look forward to working with BHCC and the other prestigious trial sites we will be activating across the U.S. Importantly, we are on target to dose our first patient, and we expect to have early tolerability and safety data from this patient available by the end of 2023," stated Pietro Bersani, Chief Executive Officer of Kiromic BioPharma. "We plan to assess preliminary efficacy by end of January 2024, and complete the dose-escalation portion of the study by the second half of 2024, at which point we expect to have sufficient evidence supporting the tolerability and the efficacy of Deltacel. These are crucial steps forward as we advance our goal to bring a transformative new treatment to patients with advanced NSCLC."

About Deltacel (KB-GDT-01)

Deltacel (KB-GDT-01) is an investigational gamma delta T-cell (GDT) therapy currently in the Deltacel-01 Phase 1 trial for the treatment of non–small cell lung cancer. An allogeneic product consisting of unmodified, donor-derived gamma delta T cells, Deltacel is Kiromic BioPharma’s lead candidate in its GDT platform. Deltacel is designed to exploit the natural potency of GDT cells to target solid cancers, with an initial focus on NSCLC, the most prevalent type of lung cancer and representing about 80% to 85% of lung cancer cases. Data from two preclinical studies demonstrated Deltacel’s favorable safety and efficacy profile when it was combined with low-dose radiation.

About Beverly Hills Cancer Center

As a private, academic, community-based cancer center, Beverly Hills Cancer Center not only provides state-of-the-art cancer treatment modalities all under one roof, but also leading clinical trials and research for cancer that are offered at very few centers in the world, attracting patients globally and saving lives. By providing access to groundbreaking clinical trials, the Beverly Hills Cancer Center offers patients the opportunity to participate in the most advanced cancer treatments in development in the world. Beverly Hills Cancer Center is comprised of an internationally recognized multidisciplinary medical team consisting of medical oncologists, radiation oncologists, radiologists, hematologists, and internists who provide exceptional patient care and support services including a robust and highly efficient team of clinical research professionals. For more information, visit: www.bhcancercenter.com.

Kinnate Biopharma Inc. Reports Third Quarter 2023 Financial Results and Recent Corporate Updates

On November 9, 2023 Kinnate Biopharma Inc. (Nasdaq: KNTE) ("Kinnate" or the "Company"), a clinical-stage precision oncology company, reported financial results for the third quarter of 2023 and recent corporate updates (Press release, Kinnate Biopharma, NOV 9, 2023, View Source [SID1234637376]).

Nima Farzan, chief executive officer of Kinnate Biopharma Inc., stated, "Following the announcement of the Company’s strategic reprioritization, we are focused on advancing our pan-RAF inhibitor exarafenib in combination with binimetinib and our c-MET inhibitor KIN-8741, and are focusing our discovery efforts around our CDK4 selective inhibitor program. We remain committed to pursuing therapies that can improve outcomes and make a positive impact on patients’ lives while also maximizing value for our shareholders."

Previously Announced Strategic Reprioritization and Pipeline Updates

Kinnate previously announced a strategic reprioritization and workforce restructuring based on a strategic review of its business (View Release).
As a result of the reprioritization, the Company is prioritizing the exarafenib combination, KIN-8741 and discovery efforts around its CDK4 selective program.
Dose exploration for the combination of exarafenib, the Company’s investigational pan-RAF inhibitor, and binimetinib is currently underway in the KN-8701 clinical trial, with a primary focus on NRAS mutant melanoma. In the fourth quarter of 2023, the Company intends to select two doses for further development.
Kinnate expects to file an Investigational New Drug ("IND") application for KIN-8741, the Company’s investigational c-MET inhibitor, with the U.S. Food and Drug Administration in the fourth quarter of 2023.
Kinnate is evaluating lead potentially brain-penetrant, selective CDK4 inhibitors for potential selection as a drug candidate and expects to nominate a drug candidate in the fourth quarter of 2023.
Additionally, as part of the reprioritization plan, Kinnate previously announced it will not initiate a clinical trial for KIN-7136, the Company’s investigational MEK inhibitor, and will explore strategic alternatives for exarafenib monotherapy and KIN-3248, an investigational FGFR inhibitor.
Kinnate implemented a workforce restructuring to align with its refined focus, reducing the Company’s workforce by approximately 70%. The Company is also taking related measures to reduce operating expenses.
Financial Results

As of September 30, 2023, total cash, cash equivalents and investments were $180.3 million, which is expected to fund current operations into at least the second quarter of 2026.
Third quarter research and development expenses for 2023 were $24.5 million, compared to $23.5 million for the same period in 2022.
Third quarter general and administrative expenses for 2023 were $6.6 million, compared to $7.8 million for the same period in 2022.
Third quarter operating expenses for 2023 included $2.0 million of restructuring costs.
Third quarter net loss for 2023 was $30.7 million, compared to $30.7 million for the same period in 2022.

Intellia Therapeutics Announces Third Quarter 2023 Financial Results and Highlights Recent Company Progress

On November 9, 2023 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage genome editing company focused on developing potentially curative therapies leveraging CRISPR-based technologies, reported operational highlights and financial results for the third quarter ended September 30, 2023 (Press release, Intellia, NOV 9, 2023, View Source [SID1234637375]).

"2023 has been a year of remarkable progress in which Intellia received two IND clearances for investigational in vivo CRISPR therapies. With the imminent start of the NTLA-2001 MAGNITUDE Phase 3 trial, Intellia has now become a late-stage drug development company," said Intellia President and Chief Executive Officer John Leonard, M.D. "Looking ahead, we expect to achieve several notable milestones in the coming weeks and months, including completing enrollment of the NTLA-2002 Phase 2 study in people with hereditary angioedema and submitting a regulatory filing to begin clinical development for NTLA-3001, our in vivo gene insertion program for people living with alpha-1 antitrypsin deficiency. We look forward to advancing our pipeline and platform as we move closer to realizing the potential of CRISPR-based medicines."

Third Quarter 2023 and Recent Operational Highlights

In Vivo Program Updates

Transthyretin (ATTR) Amyloidosis

NTLA-2001: NTLA-2001 is an in vivo, systemically delivered, investigational CRISPR-based therapy designed to inactivate the TTR gene in liver cells and thereby prevent the production of transthyretin (TTR) protein for the treatment of ATTR amyloidosis. NTLA-2001 offers the possibility of halting and reversing the disease by driving a deep, consistent and potentially lifelong reduction in TTR protein after a single dose. NTLA-2001 is subject to a co-development/co-promotion agreement between Intellia, the lead party for this program, and Regeneron.
ATTR Amyloidosis with Cardiomyopathy (ATTR-CM):
The Company announced in October that the U.S. Food and Drug Administration (FDA) cleared the NTLA-2001 Phase 3 Investigational New Drug (IND) application for the treatment of ATTR-CM. The MAGNITUDE pivotal Phase 3 trial is a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of NTLA-2001 in approximately 765 patients with ATTR-CM. The primary endpoint of the study is a composite endpoint of cardiovascular (CV)-related mortality and CV-related events. Patients will be randomized 2:1 NTLA-2001:placebo, with a single 55 mg infusion of NTLA-2001 administered. The Company expects to initiate the study by year-end with patient dosing to commence early 2024.
Hereditary ATTR Amyloidosis with Polyneuropathy (ATTRv-PN):
The Company is actively preparing for a global pivotal Phase 3 study of NTLA-2001 for the treatment of ATTRv-PN, including discussions with regulatory authorities.
Updated Data from NTLA-2001 Phase 1 Study
In November, Intellia announced new positive interim results from the Phase 1 study of NTLA-2001. Updated data from over 60 patients showed consistent, deep and durable serum TTR reduction achieved with a single dose of NTLA-2001, including 29 patients who reached 12 months or more of follow-up as of the data cut-off date of May 11, 2023. Across all patients who received a dose of 0.3 mg/kg or higher (n=62), the median serum TTR reduction was 91% and the median absolute residual serum TTR concentration was 17 µg/mL at day 28. Across all patients and at all dose levels tested, NTLA-2001 was generally well tolerated, and the majority of adverse events were mild in severity. These interim data were presented at the 4th International ATTR Amyloidosis Meeting, held in Madrid, Spain.
Hereditary Angioedema (HAE)

NTLA-2002: NTLA-2002 is a wholly owned, in vivo, systemically delivered investigational CRISPR-based therapy. NTLA-2002 is designed to knock out the KLKB1 gene in the liver, with the potential to permanently reduce total plasma kallikrein protein and activity, a key mediator of HAE. This investigational approach aims to prevent attacks for people living with HAE by providing continuous reduction of plasma kallikrein activity, following a single dose. It also aims to eliminate the significant treatment burden associated with currently available HAE therapies. NTLA-2002 is being evaluated in a Phase 1/2 study in adults with Type I or Type II HAE.
In October, Intellia announced that the European Medicines Agency (EMA) granted Priority Medicine (PRIME) designation to NTLA-2002 for the treatment of HAE. PRIME designation is granted by the EMA to drug candidates that may offer a major therapeutic advantage over existing treatments or that benefit patients without treatment options.
Following the identification of all patients, Intellia is on track to complete enrollment in the Phase 2 portion of the Phase 1/2 study in Q4 2023.
Intellia plans to initiate the global pivotal Phase 3 study, including U.S. patients, as early as the third quarter of 2024, subject to regulatory feedback.
Alpha-1 Antitrypsin Deficiency (AATD)

NTLA-3001 for AATD-Associated Lung Disease: NTLA-3001 is a wholly owned, first-in-class CRISPR-mediated in vivo targeted gene insertion development candidate for the treatment of AATD-associated lung disease. It is designed to precisely insert a healthy copy of the SERPINA1 gene, which encodes the alpha-1 antitrypsin (A1AT) protein, with the potential to restore permanent expression of functional A1AT protein to therapeutic levels after a single dose. This approach seeks to improve patient outcomes, including eliminating the need for weekly intravenous infusions of A1AT augmentation therapy or lung transplant in severe cases.
Intellia plans to submit a Clinical Trial Application (CTA) in Q1 2024 to initiate a first-in-human, Phase 1 study of NTLA-3001.
NTLA-2003 for AATD-Associated Liver Disease: NTLA-2003 is a wholly owned, in vivo knockout development candidate for the treatment of AATD-associated liver disease. It is designed to inactivate the SERPINA1 gene responsible for the production of abnormal A1AT protein in the liver.
Based on a prioritization of resources, the Company is making a strategic shift to halt further IND-enabling activities for NTLA-2003 to advance an AATD research-stage program leveraging the Company’s DNA writing technology.
Ex Vivo Program Updates

Intellia is advancing multiple preclinical programs, wholly owned and in collaboration with partners, utilizing its allogeneic platform for the treatment of immuno-oncology and autoimmune diseases. The Company’s proprietary allogeneic cell engineering platform is designed to avoid both T cell- and NK cell-mediated rejection, a key unsolved challenge with other investigational allogeneic approaches.
Platform and Pipeline Expansion

As Intellia’s DNA writing technology has met key internal research milestones, the Company will now prioritize the advancement of a research-stage program for the treatment of AATD.
In October, Intellia and Regeneron announced an expanded research collaboration to develop additional in vivo CRISPR-based gene editing therapies focused on neurological and muscular diseases. The collaboration will leverage Regeneron’s proprietary antibody-targeted adeno-associated virus (AAV) vectors and delivery systems and Intellia’s proprietary Nme2 CRISPR/Cas9 (Nme2Cas9) systems adapted for viral vector delivery and designed to precisely modify a target gene.
Additionally, Regeneron has exercised its option to extend the existing technology collaboration term with Intellia for two years. The technology collaboration term now extends to April 2026, and Intellia will receive a $30 million payment in the first half of 2024.
In September, SparingVision announced that it had selected a second target as part of its strategic collaboration with Intellia to develop novel genomic medicines, utilizing CRISPR-based gene editing technologies for the treatment of ocular diseases.
Upcoming Event

The Company will participate in the Jefferies London Healthcare Conference, taking place November 14-16 in London.

Upcoming Milestones

The Company has set forth the following expected milestones for pipeline progression:

NTLA-2001 for ATTR amyloidosis:
Initiate a global pivotal study for NTLA-2001 for ATTR-CM by year-end 2023.
Prepare for a Phase 3 study of NTLA-2001 for the treatment of ATTRv-PN, including discussions with regulatory authorities.
NTLA-2002 for HAE:
Complete enrollment in the Phase 2 portion of the Phase 1/2 study in Q4 2023.
NTLA-3001 for AATD:
Submit a CTA application for NTLA-3001 for AATD-associated lung disease in Q1 2024.
Platform Innovation:
Advance novel gene editing technologies, including DNA writing and delivery to other tissues outside of the liver.
Third Quarter 2023 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $992.5 million as of September 30, 2023, compared to $1.3 billion as of December 31, 2022. The decrease was driven by cash used to fund operations of $343.2 million. The decrease was offset in part by $37.4 million of interest income, $12.6 million of reimbursement from its collaborators, $16.2 million of net equity proceeds from the Company’s "At the Market" (ATM) program and $7.7 million in proceeds from employee-based stock plans.
Collaboration Revenue: Collaboration revenue decreased by $1.3 million to $12.0 million during the third quarter of 2023, compared to $13.3 million during the third quarter of 2022.
R&D Expenses: Research and development expenses increased by $17.0 million to $113.7 million during the third quarter of 2023, compared to $96.7 million during the third quarter of 2022. This increase was primarily driven by the advancement of our lead programs and personnel growth to support these programs. Stock-based compensation expense included in research and development expenses was $21.2 million for the third quarter of 2023.
G&A Expenses: General and administrative expenses increased by $7.3 million to $29.4 million during the third quarter of 2023, compared to $22.1 million during the third quarter of 2022. This increase was primarily related to an increase in stock-based compensation of $5.3 million. Stock-based compensation expense included in general and administrative expenses was $14.1 million for the third quarter of 2023.
Net Loss: The Company’s net loss was $122.2 million for the third quarter of 2023, compared to $113.2 million during the third quarter of 2022.
Conference Call to Discuss Third Quarter 2023 Results

The Company will discuss these results on a conference call today, Thursday, November 9 at 8 a.m. ET.
To join the call:

U.S. callers should dial 1-833-316-0545 and international callers should dial 1-412-317-5726, approximately five minutes before the call. All participants should ask to be connected to the Intellia Therapeutics conference call.
Please visit this link for a simultaneous live webcast of the call.
A replay of the call will be available through the Events and Presentations page of the Investors & Media section on Intellia’s website at intelliatx.com, beginning on November 9 at 12 p.m. ET.