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]).

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"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.

On November 9, 2023 INOVIO (NASDAQ:INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, reported its financial results and operational highlights for the third quarter ended September 30, 2023 (Press release, Inovio, NOV 9, 2023, View Source [SID1234637374]).

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"The past quarter has seen significant progress for our lead candidate, INO-3107, for the treatment of Recurrent Respiratory Papillomatosis, or RRP," said INOVIO’s President and Chief Executive Officer, Dr. Jacqueline Shea. "Following Breakthrough Therapy designation from the FDA in September and subsequent feedback that we no longer need to complete a Phase 3 trial prior to submitting a BLA under the accelerated approval program, our team is laser-focused on next steps. These steps include holding an Initial Comprehensive Multidisciplinary Breakthrough Therapy Meeting with the FDA in the near future to confirm alignment on our accelerated development plans and to clarify timing associated with potentially making INO-3107 available to patients suffering from this devastating disease."

Shea continued: "The progress we have achieved with INO-3107 exemplifies the strategy we have been implementing over the past year, as we have focused on advancing late-stage candidates and driving toward near, mid- and long-term milestones for our pipeline. In the past 18 months, we have reshaped our company, reduced our operating spend and reprioritized our pipeline with INO-3107 as our lead candidate. I am more confident than ever that our experienced team is prepared to deliver on the next critical steps of development and on the promise of DNA medicine for patients."

INOVIO’s Chief Commercial Officer, Mark Twyman, stated: "Now that we are moving toward a BLA submission on an accelerated timeline, we are advancing our commercialization strategy expeditiously. We are implementing all aspects of our plan, including strategies for distribution, payor, specialty pharmacy and field force design, with the goal of being ready to launch rapidly if we receive approval. We are also continuing to deepen our understanding of the RRP market and applying what we have learned from our discussions with healthcare providers and RRP patients. Delivering on this opportunity now is incredibly important for patients suffering from RRP as INO-3107 represents a significant improvement in therapeutic options over the current standard of care."

Regulatory Status of INO-3107
The FDA granted Breakthrough Therapy designation to INOVIO’s lead candidate based on clinical evidence indicating INO-3107 may demonstrate substantial improvement over existing therapies for RRP. Breakthrough Therapy designation was created by the FDA to help expedite the development and review of drug candidates that are intended to treat a serious or life-threatening condition and for which preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).

INOVIO also received feedback from the FDA that data from its completed Phase 1/2 trial of INO-3107 could support INOVIO’s submission of a BLA for review under the FDA’s accelerated approval program. The FDA advised that completion of a Phase 3 trial would not be required to support this submission. INOVIO will be required to initiate a confirmatory trial prior to BLA submission for accelerated approval and satisfy all other FDA filing requirements. Subsequent to this feedback, INOVIO has been focused on preparing to file its BLA under the accelerated approval program. The company anticipates additional meetings with the FDA to finalize next steps, including an Initial Comprehensive Multidisciplinary Breakthrough Therapy Meeting, or Type B meeting, which it has requested to be held in the fourth quarter of 2023. INOVIO plans to pursue other benefits offered by Breakthrough Therapy designation to quickly resolve any future questions, as well as take advantage of the opportunity to submit under the FDA’s Rolling Review program and request a Priority Review once the BLA is fully submitted.

Commercialization Plans for INO-3107
INOVIO has accelerated its commercialization strategy for INO-3107 as a potential treatment for RRP as a result of the opportunity to file its BLA under the FDA’s accelerated approval program. This includes implementing its plans for product distribution and logistics, payor engagement and reimbursement, specialty pharmacy identification, patient and provider awareness and education, customer service programs, and other sales and marketing activities. The company has an experienced commercial team that is actively engaging external partners and service providers to be prepared for launch, should INO-3107 receive regulatory approval.

As part of its commercialization plans, INOVIO is continuing to deepen its market understanding of RRP as a disease and the treatment paradigm in the United States. RRP is a chronic, rare disease caused by HPV-6 and HPV-11. The current standard of care is surgery, with many patients facing a lifetime of repeated surgeries as their only option. The most widely cited U.S. epidemiology data estimated that there were approximately 14,000 active cases of RRP in the United States. A recent publication cites that on average, patients with RRP undergo about 4 surgeries per year.

Based on its ongoing market research, INOVIO believes that laryngologists are the primary healthcare providers treating patients suffering from this condition and that they are comfortable administering drugs and utilizing new tools and devices. The company estimates that approximately 300 to 400 laryngologists conduct the majority of RRP surgical procedures in the United States. Key opinion leaders estimate that approximately one-half of all laryngologists practice in academic institutions. In recent discussions with patients, INOVIO believes that RRP patients may prefer to be treated at these regional academic centers.

About INO-3107
INO-3107 is INOVIO’s lead DNA medicine product candidate and is being developed as a potential treatment for RRP. INO-3107 is designed to elicit an antigen targeted T cell response against HPV-6 and HPV-11, the HPV types responsible for causing RRP, among other HPV-related diseases. These targeted T cells are designed to seek out and kill HPV-6 and HPV-11 infected cells, with the aim of potentially preventing or slowing the growth of new papillomas. In addition to being designated a Breakthrough Therapy, INO-3107 has also received Orphan Drug designation from the European Commission and from the FDA.

In a Phase 1/2 clinical trial conducted with INO-3107, 81.3% (26/32) of patients had a decrease in surgical interventions in the year after INO-3107 administration compared to the prior year, including 28.1% (9/32) that required no surgical intervention during or after the dosing window. Patients in the trial had a median range of 4 surgeries (2-8) in the year prior to dosing. After dosing, there was a median decrease of 3 surgical interventions (95% confidence interval -3, -2). At the outset of the study (Day 0), patients could have RRP tissue surgically removed, but any surgery performed after Day 0 during the dosing window was counted against the efficacy endpoint. Treatment with INO-3107 generated a strong immune response in the trial, inducing activated CD4 T cells and activated CD8 T cells with lytic potential. T-cell responses were also observed at Week 52, indicating a persistent cellular memory response. INO-3107 was well tolerated by participants in the trial, resulting in mostly low-grade (Grade 1) treatment-emergent adverse effects such as injection site pain and fatigue.

Advancing INOVIO’s Three-Part Strategy to Develop its Pipeline
Since mid-2022, INOVIO has been advancing a three-part strategy to deliver on the promise of DNA medicines and the product candidates in its pipeline. In the near-term, INOVIO is focused on optimizing the opportunity for INO-3107 as a potential treatment for RRP patients. In the mid-term, INOVIO is working to advance eight other clinical-stage candidates targeting a number of HPV-related diseases, cancers and infectious diseases. For the longer term, INOVIO is developing next-generation DNA medicine technology, including DNA encoded monoclonal antibodies (dMAbs) targeting COVID-19, as well as DNA-launched nanoparticles (dLNPs) targeting infectious diseases and cancer vaccines that have various disease targets. INOVIO’s commitment to financial discipline and leveraging strong partnerships are also key components to its corporate strategy.

Third Quarter 2023 Financial Results

Cash, Cash Equivalents and Short-term Investments: As of September 30, 2023, cash, cash equivalents and short-term investments were $167.5 million compared to $253.0 million as of December 31, 2022.

Revenues: Total revenues for the three months ended September 30, 2023 were $388,000, compared to $9.2 million for the same period in 2022. The revenue generated in the third quarter of 2022 was associated with a Procurement Contract with the U.S. Department of Defense for INOVIO’s devices and accessories to be used for delivery of its COVID-19 vaccine candidate, INO-4800, which the company has discontinued.

Research and Development (R&D) Expenses: R&D expenses for the three months ended September 30, 2023 were $15.5 million compared to $33.1 million for the same period in 2022. The decrease in R&D expenses was primarily the result of lower drug manufacturing, clinical trial expenses and outside services related to INO-4800 and other COVID-19 studies and lower employee and consultant compensation, including stock-based compensation, among other variances.

General and Administrative (G&A) Expenses: G&A expenses for the 2023 third quarter were $9.9 million compared to $11.8 million for the same period in 2022.

Total Operating Expenses: Total operating expenses were $35.9 million compared to $44.9 million for the same period in 2022. During the three months ended September 30, 2023, the company recognized a non-cash goodwill impairment charge of $10.5 million.

Net Loss: INOVIO’s net loss for the quarter ended September 30, 2023 was $33.9 million, or $0.13 per basic and diluted share, compared to net loss of $37.8 million, or $0.15 per basic and diluted share, for the third quarter of 2022. Excluding the non-cash goodwill impairment expense, net loss for the quarter ended September 30, 2023 would have been $23.4 million, or $0.09 per basic and diluted share.

Shares Outstanding: As of September 30, 2023, INOVIO had 269.7 million common shares outstanding and 290.6 million common shares outstanding on a fully diluted basis, after giving effect to the exercise, vesting and conversion, as applicable, of its outstanding options, restricted stock units, convertible preferred stock, and convertible debt.
INOVIO’s balance sheet and statement of operations are provided below. Additional information is included in INOVIO’s quarterly report on Form 10-Q for the quarter ended September 30, 2023, which can be accessed at: View Source

Cash Guidance
Following feedback from the FDA on the accelerated approval pathway for INO-3107, INOVIO now estimates its cash runway to extend into the second quarter of 2025. This projection includes a cash burn estimate of approximately $26 million for the fourth quarter of 2023. These cash projections do not include any funds that may be raised through the Company’s existing at-the-market program or other capital-raising activities.

Conference Call / Webcast Information
INOVIO’s management will host its quarterly conference call and webcast at 4:30 p.m. ET today. A replay of the conference call will be available following the conclusion of the call. The live webcast and replay may be accessed by visiting INOVIO’s website at View Source

About INOVIO’s DNA Medicines Platform
INOVIO’s DNA medicines platform has two innovative components: precisely designed DNA plasmids, delivered by INOVIO’s proprietary investigational medical device, CELLECTRA. INOVIO uses proprietary technology to design its DNA plasmids, which are small circular DNA molecules that work like software the body’s cells can download to produce specific proteins to target and fight disease. INOVIO’s CELLECTRA delivery devices help ensure its DNA medicines enter the body’s cells for optimal effect, without chemical adjuvants or nanoparticles and without the risk of the anti-vector response seen in viral vector platforms.

On November 9, 2023 Inhibrx, Inc. (Nasdaq: INBX), or Inhibrx, or the Company, a biopharmaceutical company with four programs in ongoing clinical trials and a strong emerging pipeline, reported financial results for the third quarter of 2023 and provided an update on recent corporate highlights (Press release, Inhibrx, NOV 9, 2023, View Source [SID1234637373]).

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Recent Corporate Highlights
•On August 29, 2023, Inhibrx announced that it had entered into a securities purchase agreement, or the Purchase Agreement, for a private placement financing, or the PIPE, resulting in gross proceeds of approximately $200.0 million. Pursuant to the Purchase Agreement, the Company sold and issued to certain institutional and other accredited investors, or the Purchasers, 3,621,314 shares of its common stock at a purchase price of $19.35 per share and, with respect to certain Purchasers, pre-funded warrants to purchase 6,714,636 shares of its common stock at a purchase price of $19.3499 per pre-funded warrant, which have an exercise price of $0.0001 per share.
•On September 19, 2023, Inhibrx announced that it had retained full global rights to INBRX-101 as a result of Chiesi Farmaceutici S.p.A declining to exercise its option for the ex-North American rights to develop and commercialize INBRX-101 for the treatment of patients with emphysema due to Alpha-1 Antitrypsin Deficiency, or AATD.
•On November 2, 2023, Inhibrx announced preliminary efficacy and safety data at the Annual Connective Tissue Oncology Society (CTOS) Conference from the Phase 1 trial of INBRX-109 in combination with Irinotecan (IRI) and Temozolomide (TMZ) for the treatment of advanced or metastic, unresectable Ewing sarcoma. Among the 13 patients evaluable as of the data cut of September 8, 2023, the observed disease control rate was 76.9%, or 10 out of 13 patients as measured by RECISTv1.1, with 7 patients achieving partial responses (53.8%) and 3 patients achieving stable disease (23.1%). Durable clinical benefit was observed in 4 patients (30.8%) who achieved disease control lasting greater than 6 months. Overall, INBRX-109 in combination with IRI/TMZ was well tolerated. The most common adverse events were diarrhea, nausea and fatigue, all consistent with the known safety profile of IRI/TMZ.
Financial Results
•Cash and Cash Equivalents. As of September 30, 2023, Inhibrx had cash and cash equivalents of $337.3 million, compared to $192.5 million at June 30, 2023. During the third quarter of 2023, the Company received gross proceeds of $200.0 million from the PIPE. These proceeds were offset in part by cash outflows from operations, which increased during the third quarter of 2023 primarily due to the following activity:
◦a large upfront payment made to one of the Company’s contract development and manufacturing organizations, or CDMOs, for the prepayment of raw materials for future manufacturing runs, as well as other increased development and manufacturing costs to support its clinical candidates; and

◦the Company’s payments to its contract research organizations, or CRO, partners continue to increase as the registration-enabling Phase 2 trials progress for both INBRX-101 for the treatment of emphysema due to AATD and INBRX-109 for the treatment of unresectable or metastatic conventional chondrosarcoma, and additional cash outlay to its CRO partners for the INBRX-105 and INBRX-106 Phase 1/2 trials.
•R&D Expense. Research and development expenses were $38.1 million during the third quarter of 2023, compared to $24.9 million during the third quarter of 2022. The increase in research and development expenses was primarily due to the following factors:
◦an increase in clinical trial expenses, primarily related to the registration-enabling Phase 2 trial for INBRX-101 for the treatment of emphysema due to AATD, which was initiated during the current year, as well as the progression of its INBRX-109 registration-enabling Phase 2 trial for the treatment of unresectable or metastatic conventional chondrosarcoma;
◦an increase in CMC expenses due to the nature of the development and manufacturing activities performed at its CDMO and CRO partners supporting the Company’s clinical and preclinical therapeutic candidates, which reflect the stage-specific needs of its programs during each period, including early and late stage drug substance clinical manufacturing, drug product manufacturing, and selected biologics license applications-enabling activities; and
◦an increase in personnel-related costs, partially attributable to an increase in headcount as the Company continues to expand its clinical teams, as well as the issuance of additional stock options and the expansion of the Company’s bonus eligibility pool in the current year.
•G&A Expense. General and administrative expenses were $7.9 million during the third quarter of 2023, compared to $5.3 million during the third quarter of 2022. The increase in general and administrative expenses was primarily due to the following factors:
◦an increase in additional personnel-related costs in part due to the expansion of the Company’s commercial strategy and medical affairs team as well as the issuance of additional stock options and the expansion of its bonus eligibility pool in the current year;
◦an increase in consulting services supporting the Company’s commercial operations business intelligence strategies, as well as market research and other scientific publication expenses incurred related to the Company’s continued pre-commercialization efforts for INBRX-101 and INBRX-109; and
◦an increase in professional service expenses related to accounting and legal services which support the Company in its general corporate and intellectual property matters.
•Net Loss. Net loss was $51.8 million during the third quarter of 2023, or $1.10 per share, compared to $35.3 million during the third quarter of 2022, or $0.90 per share.

On November 9, 2023 IN8bio, Inc. (Nasdaq: INAB), a leading clinical-stage biopharmaceutical company developing innovative gamma-delta T cell therapies, reported financial results, operational highlights and recent corporate developments for the third quarter ended September 30, 2023 (Press release, In8bio, NOV 9, 2023, View Source [SID1234637372]).

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"We have continued to execute and to make impressive clinical progress across the breadth of our pipeline, which we shared at our recent Research & Development Day," said William Ho, CEO and co-founder of IN8bio. "Having completed enrollment in the dose escalation portion of the Phase 1 trial of INB-100 in hematologic malignancies and initiated enrollment for the Phase 2 trial of INB-400 in newly diagnosed glioblastoma, we are making strides towards our mission of exploring the full potential of gamma-delta T cells as a much-needed treatment option for cancer patients. We are encouraged by the positive data we have seen thus far and are excited to share additional clinical updates on our INB-100 and INB-200 programs at the upcoming SNO and ASH (Free ASH Whitepaper) meetings."

Business Highlights and Recent Developments

Presented two posters reporting biologic correlative data from the ongoing Phase 1 clinical trial of INB-200 in GBM and preclinical data on IN8bio’s iPSC gamma-delta T cell platform at SITC (Free SITC Whitepaper). The data presented from the INB-200 trial demonstrate the potential of single and repeat doses of DeltEx drug-resistant immunotherapy (DRI) to induce T cell persistence and sustained immune responses. Updated patient, enrollment and survival data from the ongoing INB-200 study will be presented at the SNO Annual Meeting on November 17, 2023. Data from IN8bio’s iPSC platform demonstrate the ability to kill multiple cancer types including ovarian cancer, GBM, CML and AML cell lines along with the potential to generate billions of iPSC-derived Vδ1+ T cells.

Completed dose escalation in the Phase 1 Trial of INB-100 in leukemia patients and will present clinical data at the upcoming ASH (Free ASH Whitepaper) Annual Meeting on December 11, 2023. Enrollment in the dose escalation phase of the Phase 1 clinical trial (NCT03533816) of INB-100 is now closed. The presentation at ASH (Free ASH Whitepaper) will highlight clinical data updating the efficacy results of INB-100 including complete responses (CRs) and durability.

Initiated enrollment for the company-sponsored Phase 2 trial of INB-400 in GBM. The Phase 2 clinical trial of INB-400 (NCT05664243), a genetically engineered gamma-delta T cell therapy, is open for enrollment and plans to enroll approximately 40 patients in "Arm A" of the study, in which autologous gamma delta cells will be used to treat patients with newly diagnosed GBM. The primary endpoint of the study is 12-month overall survival (OS) rate, and key secondary endpoints include tolerability, progression-free survival (PFS), overall response rate (ORR) and time to progression (TTP). The University of Louisville and The Cleveland Clinic are the first clinical sites activated to enroll patients. The company will present a poster at the SNO Annual Meeting.

Hosted R&D Day on October 12, 2023, highlighting IN8bio’s unique Gamma-Delta T cell platform. The event offered the opportunity to gain Key Opinion Leader (KOL) insights into IN8bio’s clinical programs. Featured presentations included those from IN8bio’s management team on gamma-delta T cells, IN8bio’s manufacturing capabilities, an overview of the INB-100, INB-200, and INB-400 clinical programs, as well as presentations from key oncology thought leaders Leo Luznik, M.D., Professor of Oncology at Johns Hopkins Medicine and Michael Bishop, M.D., Director of the David and Etta Jones Center for Cellular Therapy at the University of Chicago, featuring the topics of allogeneic transplantation and the challenges of leukemic relapse. A replay of the webcast event can be found here.

Upcoming Pipeline Milestones and Events

INB-100: Presenting updated Phase 1 trial clinical data from patients with hematological malignancies undergoing HSCT at the ASH (Free ASH Whitepaper) Annual Meeting on December 11, 2023.
INB-200: Complete enrollment of Cohort 3 in the Phase 1 trial; will present updated data at SNO on November 17, 2023 with longer-term follow-up at medical meetings throughout 2024.
INB-300: Present additional preclinical data demonstrating proof-of-concept for the nsCAR platform targeting CD33 and CD123 at a medical meeting in first half of 2024.
INB-400: Present a poster at the SNO Annual Meeting on November 17, 2023; file investigational new drug (IND) application for allogeneic arms (Arms B and C) of the Phase 2 trial in newly diagnosed and relapsed GBM in 2024.

Third Quarter 2023 Financial Highlights

Research and Development expenses: Research and development expenses were $3.8 million for the three months ended September 30, 2023, compared to $4.3 million for the comparable prior year period. The decrease was primarily due to a reduction in contract research organization expenses for INB-400 related to the IND filing in the prior year period, partially offset by increased personnel-related costs, including salaries, benefits, and non-cash stock-based compensation due to increased headcount.

General and administrative expenses: General and administrative expenses were $3.4 million for the three months ended September 30, 2023, compared to $3.1 million for the comparable prior year period. The increase was primarily due to an increase in professional services.

Net Loss: The Company reported a net loss of $7.2 million, or $0.23 per basic and diluted common share, for the three months ended September 30, 2023, compared to $7.4 million, or $0.34 per basic and diluted common share, for the comparable prior year period.

Cash: As of September 30, 2023, the Company had cash of $12.9 million, compared to $17.0 million as of June 30, 2023.

On November 9, 2023 Illumina, Inc. reported its financial results for the third quarter of fiscal year 2023, which include the consolidated financial results for GRAIL (Press release, Illumina, NOV 9, 2023, View Source [SID1234637371]).

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"While the environment remains challenging, I am confident in our ability to navigate it and position the company for long-term success," said Jacob Thaysen, Chief Executive Officer. "I came to Illumina for the opportunity presented by our core business. While I evaluate the company’s strategy, we will remain focused on driving on further placements of the NovaSeq X, which will boost consumables demand. We will also continue optimizing our operations and drive stronger execution."

Third quarter consolidated results
GAAP Non-GAAP (a)
Dollars in millions, except per share amounts Q3 2023 Q3 2022 Q3 2023 Q3 2022
Revenue $ 1,119 $ 1,115 $ 1,119 $ 1,115
Gross margin 61.1 % 64.3 % 65.4 % 68.4 %
Research and development ("R&D") expense $ 315 $ 325 $ 312 $ 324
Selling, general and administrative ("SG&A") expense $ 303 $ 146 $ 328 $ 336
Goodwill and intangible impairment
$ 821 $ 3,914 $ — $ —
Legal contingency and settlement $ (1) $ (11) $ — $ —
Operating (loss) profit $ (754) $ (3,657) $ 93 $ 102
Operating margin (67.3) % (327.9) % 8.3 % 9.2 %
Tax (benefit) provision
$ (28) $ 144 $ 35 $ 40
Tax rate 3.6 % (4.0) % 39.7 % 43.2 %
Net (loss) income $ (754) $ (3,816) $ 52 $ 54
Diluted (loss) earnings per share $ (4.77) $ (24.26) $ 0.33 $ 0.34

(a) See the tables included in the "Results of Operations – Non-GAAP" section below for reconciliations of these GAAP and non-GAAP financial measures.
During the third quarter of 2023, the company recognized $712 million in goodwill and $109 million in intangible asset (IPR&D) impairment related to the GRAIL segment. The goodwill impairment was primarily due to a decrease in the company’s consolidated market capitalization and a higher discount rate selected for the fair value calculation of the GRAIL reporting unit. The IPR&D impairment was primarily due to a decrease in projected cash flows and a higher discount rate selected for the fair value calculation of the GRAIL IPR&D asset. During the third quarter of 2022, the company recognized $3.91 billion in goodwill impairment related to the GRAIL segment.

Capital expenditures for free cash flow purposes were $45 million for Q3 2023. Cash flow provided by operations was $139 million, compared to cash flow used in operations of $(52) million in the prior year period, which included a one-time payment related to the litigation settlement with BGI. Free cash flow (cash flow provided by (used in) operations less capital expenditures) was $94 million for the quarter, compared to $(119) million in the prior year period. Depreciation and amortization expenses were $108 million for Q3 2023. At the close of the quarter, the company held $933 million in cash, cash equivalents and short-term investments. During the third quarter of 2023, the company used $750 million in cash to repay the outstanding principal of convertible notes that matured in August 2023.

Third quarter segment results
Illumina has two reportable segments, Core Illumina and GRAIL.

Core Illumina
GAAP Non-GAAP (a)
Dollars in millions Q3 2023 Q3 2022 Q3 2023 Q3 2022
Revenue (b)
$ 1,106 $ 1,110 $ 1,106 $ 1,110
Gross margin (c)
64.7 % 67.9 % 66.0 % 68.9 %
R&D expense $ 238 $ 253 $ 235 $ 252
SG&A expense $ 216 $ 66 $ 246 $ 262
Legal contingency and settlement $ (1) $ (11) $ — $ —
Operating profit
$ 262 $ 445 $ 249 $ 251
Operating margin 23.7 % 40.1 % 22.5 % 22.6 %

(a) See Table 3 included in the "Results of Operations – Non-GAAP" section below for reconciliations of these GAAP and non-GAAP financial measures.

(b) Core Illumina revenue for Q3 2023 was flat as compared to Q3 2022, and flat on a constant currency basis. Amounts for Q3 2023 and Q3 2022 included intercompany revenue of $8 million and $5 million, respectively, which is eliminated in consolidation.
(c) The year-over-year decrease in gross margin was primarily driven by less fixed cost leverage on lower manufacturing volumes, product mix, as well as lower instrument margins and higher field service and installation costs due to the NovaSeq X launch, which is typical in a launch year.

GRAIL
GAAP Non-GAAP (a)
In millions Q3 2023 Q3 2022 Q3 2023 Q3 2022
Revenue $ 21 $ 10 $ 21 $ 10
Gross (loss) profit $ (27) $ (32) $ 6 $ 1
R&D expense $ 79 $ 74 $ 79 $ 74
SG&A expense $ 87 $ 81 $ 82 $ 75
Goodwill and intangible impairment
$ 821 $ 3,914 $ — $ —
Operating loss $ (1,015) $ (4,101) $ (155) $ (148)

(a) See Table 3 included in the "Results of Operations – Non-GAAP" section below for reconciliations of these GAAP and non-GAAP financial measures.

As previously stated, Illumina is committed to moving as quickly as possible through the legal and regulatory processes associated with its acquisition of GRAIL. At this point, Illumina expects decisions on its appeals from the US Court of Appeals for the Fifth Circuit by the end of 2023 and from the European Court of Justice (ECJ) in mid-2024.

Key announcements by Illumina since Illumina’s last earnings release
•Received order from the European Commission to divest GRAIL; Illumina is committed to resolving all issues in a timely manner, with the objective of achieving the maximum value for shareholders and the best outcome for GRAIL
•Launched TruSight Oncology 500 (TSO 500) ctDNA Version 2, a liquid biopsy assay that enables comprehensive genomic profiling of circulating tumor DNA; key improvements include a faster turnaround time of less than four days, higher sensitivity with lower input requirements, and a more streamlined workflow
•Opened new office and state-of-the-art Illumina Solutions Center in Bengaluru, India to grow the genomics market in the most populous country in the world, unlocking opportunities for advancing health care and combating the effects of climate change in South Asia
•Appointed Jacob Thaysen, Ph.D. as Chief Executive Officer and Dr. Steve Barnard as Chief Technology Officer
•Launched the 25B flow cell (300-cycle kit) for the NovaSeq X, enabling customers to generate tens of thousands of whole genomes per year at the lowest cost per sample of any Illumina platform

A full list of recent Illumina announcements can be found in the company’s News Center.

Key announcements by GRAIL since Illumina’s last earnings release
•Collaboration with HCA Healthcare, Inc. to make GRAIL’s Galleri multi-cancer early detection (MCED) available to patients who meet screening criteria at select HCA Healthcare physician practices
•Published final results from PATHFINDER Study, which demonstrated that an earlier version of Galleri identified many cancer types that do not currently have recommended screening tests, enabled targeted cancer diagnostic evaluations, and supported diagnostic resolution for the majority of participants in less than three months
•Expanded pilot with Point32Health to offer Galleri to members meeting eligibility requirements, making Point32Health the first commercial health plan in the U.S. to offer Galleri in addition to recommended cancer screenings

A full list of recent GRAIL announcements can be found in GRAIL’s Newsroom.

Financial outlook and guidance
The non-GAAP financial guidance discussed below reflects certain pro forma adjustments to assist in analyzing and assessing our core operational performance, including the company’s Core Illumina and GRAIL segments. Please see our Reconciliation of Consolidated Non-GAAP Financial Guidance included in this release for a reconciliation of these GAAP and non-GAAP financial measures.

For fiscal year 2023, the company now expects consolidated revenue to decrease 2% to 3% compared to fiscal year 2022. The company now expects Core Illumina revenue to decrease 3% to 4% compared to fiscal year 2022. GRAIL revenue is now expected to be at the low end of the $90 million to $110 million range.

The company now expects GAAP diluted loss per share of $(6.67) to $(6.57) and non-GAAP diluted earnings per share of $0.60 to $0.70.

Conference call information
The conference call will begin at 2 p.m. Pacific Time (5 p.m. Eastern Time) on Thursday, November 9, 2023. Interested parties may access the live teleconference through the Investor Info section of Illumina’s website at investor.illumina.com. Alternatively, individuals can access the call by dialing 866.400.0049 or +1.323.794.2149 outside North America, both using conference ID 1991305. To ensure timely connection, please dial in at least ten minutes before the scheduled start of the call.

A replay of the conference call will be posted on Illumina’s website after the event and will be available for at least 30 days following.