On February 23, 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 fourth quarter and year ended December 31, 2022 (Press release, Intellia, FEB 23, 2023, View Source [SID1234627616]).

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"Intellia has hit the ground running with multiple milestones already achieved in early 2023. In addition to recently initiating the global Phase 2 study of NTLA-2002 outside of the U.S., we have also submitted an IND application to enable inclusion of patients in the U.S.," said Intellia President and Chief Executive Officer John Leonard, M.D. "As we look ahead, we are poised to submit an IND application for NTLA-2001 and initiate a global pivotal trial for the cardiomyopathy manifestation of ATTR amyloidosis. Additionally, we look forward to presenting new and important clinical data from the ongoing Phase 1 study, which builds on the growing body of data that support NTLA-2001’s potential to transform the ATTR amyloidosis treatment landscape for patients with cardiomyopathy or polyneuropathy. In parallel, we are advancing NTLA-3001, our first wholly owned in vivo gene insertion candidate, which may normalize levels of the missing protein in patients with alpha-1 antitrypsin deficiency. Together, we believe these efforts move us closer to setting a new standard of care for people living with serious diseases and expanding Intellia’s impact as the leading genome editing company."

Fourth Quarter 2022 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 Pharmaceuticals, Inc.
ATTR Amyloidosis with Cardiomyopathy (ATTR-CM):
Intellia announced in November 2022 positive interim results from the cardiomyopathy arm of the ongoing Phase 1 clinical trial of NTLA-2001 at the American Heart Association (AHA) Scientific Sessions 2022 held in Chicago, Illinois. The interim data from the dose-escalation portion of the study included 12 adult patients with ATTR-CM with New York Heart Association (NYHA) Class I – III heart failure. Single doses of 0.7 mg/kg and 1.0 mg/kg of NTLA-2001 led to greater than 90% mean serum TTR reductions. These deep reductions in serum TTR were sustained through the observation period, with patient follow-up ranging from four to six months. At both dose levels, NTLA-2001 was generally well-tolerated. One patient in the 0.7 mg/kg dose NYHA Class III cohort experienced a Grade 3 infusion-related reaction, which resolved without clinical sequalae. No clinically significant laboratory abnormalities were observed at either dose level.
In December 2022, the planned enrollment of the dose-expansion portion of the ATTR-CM arm was completed to support a U.S. Investigational New Drug (IND) application submission for the pivotal study. The Company anticipates submitting an IND application in mid-2023 and initiating a global pivotal trial for ATTR-CM by year-end 2023, subject to regulatory feedback.
The Company plans to present additional data from the ATTR-CM arm of the Phase 1 study in 2023, including longer-term safety and durability data, as well as emerging clinical endpoints.
Hereditary ATTR Amyloidosis with Polyneuropathy (ATTRv-PN):
During the first quarter of 2023, the planned enrollment of the dose-expansion portion of the ATTRv-PN arm in the Phase 1 study was completed to inform a pivotal study. The Company is preparing for a global pivotal study, which will include discussions with regulatory authorities.
The Company plans to present additional clinical data from the ATTRv-PN arm of the Phase 1 study in 2023.
Hereditary Angioedema (HAE)

NTLA-2002: 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.
Intellia announced in November 2022 positive interim results from an ongoing Phase 1/2 clinical study of NTLA-2002 at the American College of Allergy, Asthma & Immunology (ACAAI) 2022 Annual Scientific Meeting held in Louisville, Kentucky. The data presented were from 10 adult patients with HAE in the Phase 1, dose-escalation portion of the study. Single doses of 25 mg (n=3), 50 mg (n=4) and 75 mg (n=3) of NTLA-2002 were administered via intravenous infusion, which led to deep, dose-dependent reductions in plasma kallikrein. All patients treated in the 25 mg and 75 mg cohorts, who completed the pre-specified 16-week observation period, maintained an attack-free status through the data cut-off date (patient follow-up ranged from 2.3 to 10.6 months). Patients in the 50 mg cohort had not completed the primary 16-week observation period. At all three dose levels, NTLA-2002 was generally well-tolerated, and the majority of adverse events were mild in severity. No clinically significant laboratory abnormalities were observed.
In January 2023, Intellia was awarded the Innovation Passport for NTLA-2002 by the U.K. Medicines and Healthcare products Regulatory Agency (MHRA). The Innovation Passport is the point of entry into the U.K.’s Innovative Licensing and Access Pathway (ILAP), which is designed to accelerate time to market and facilitate patient access to innovative medicines.
Intellia announced today the initiation of patient screening in the Phase 2 portion of the Phase 1/2 of NTLA-2002 in New Zealand. The Company has selected 25 mg and 50 mg as the two, single dose levels for further evaluation in the randomized, placebo-controlled study.
Intellia announced today the Company recently submitted an IND application for NTLA-2002 to the U.S. Food and Drug Administration (FDA) to support the inclusion of U.S. sites in the Phase 2 portion of the study.
The Company plans to present additional clinical data from the Phase 1 portion of the first-in-human study in 2023, including safety, durability and attack-rate data across all three cohorts.
Alpha-1 Antitrypsin Deficiency (AATD)

NTLA-3001 for 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 is conducting IND-enabling activities for NTLA-3001 and plans to submit an IND or IND-equivalent filing in 2H 2023.
NTLA-2003 for 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. This approach aims to halt the progression of liver disease and eliminate the need for liver transplant in severe cases.
Intellia is conducting IND-enabling activities for NTLA-2003, with the expectation of completing these activities by year-end 2023.
Ex Vivo Program Updates

Immuno-oncology and Autoimmune Diseases

Intellia is advancing multiple 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.
NTLA-6001 for CD30+ Lymphomas: Intellia is identifying collaboration opportunities to advance the development of a wholly owned, allogeneic CAR-T development candidate targeting CD30.
Research and Corporate Updates

Modular Platform and Pipeline Expansion: Intellia is expanding its industry-leading genome editing platform and scientific leadership through editing, delivery and cell engineering innovations that may enable broader in vivo and ex vivo applications.
In January 2023, Intellia achieved a research milestone with its DNA writing technology. A $25.0 million milestone payment was made to shareholders of Rewrite Therapeutics in February 2023.
Sickle Cell Disease (SCD) Program Updates:
Intellia’s SCD Research Efforts: Intellia is focused on developing an in vivo editing approach for the treatment of SCD to avoid the need for bone marrow transplantation. This is a wholly owned program currently in preclinical development.
Novartis’ SCD Program: In February 2023, Novartis opted to discontinue the development of its autologous, ex vivo, CRISPR-edited hematopoietic stem cell (HSC) program targeting fetal hemoglobin (HbF) for the treatment of SCD.
Upcoming Events

The Company will participate in the following events during the first quarter of 2023:

Cowen 43rd Annual Health Care Conference, March 6, Boston
Barclays Global Healthcare Conference, March 14, Miami
Upcoming Milestones

The Company has set forth the following for pipeline progression:

NTLA-2001 for ATTR amyloidosis:
Submit an IND application in mid-2023 to enable inclusion of U.S. sites in a pivotal study of NTLA-2001 for patients with ATTR-CM.
Present additional clinical data from the ongoing Phase 1 study of NTLA-2001 in 2023.
Initiate a global pivotal NTLA-2001 trial for ATTR-CM by year-end 2023, subject to regulatory feedback.
Prepare for a Phase 3 study of NTLA-2001 for the treatment of ATTRv-PN, including discussions with regulatory authorities.
NTLA-2002 for HAE:
Present additional clinical data from the ongoing first-in-human study of NTLA-2002 in 2023.
AATD Franchise:
Submit an IND or IND-equivalent application for NTLA-3001 for AATD-associated lung disease in 2H 2023.
Complete IND-enabling activities for NTLA-2003 for AATD-associated liver disease by year-end 2023.
Platform Innovation

Advance novel gene editing technologies, including DNA writing, and delivery to other tissues outside of the liver.
Fourth Quarter and Full-Year 2022 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $1.3 billion as of December 31, 2022, compared to $1.1 billion as of December 31, 2021. The increase was driven by $337.9 million from a follow-on offering in the fourth quarter of 2022, $227.9 million of net proceeds from the Company’s "At the Market" (ATM) program and $17.2 million in proceeds from employee-based stock plans. The increase was offset in part by cash used to fund operations of approximately $372.8 million and the acquisition of Rewrite for $45.0 million.
Collaboration Revenue: Collaboration revenue increased by $0.7 million to $13.6 million during the fourth quarter of 2022, compared to $12.9 million during the fourth quarter of 2021.
R&D Expenses: Research and development expenses increased by approximately $28.9 million to $100.0 million during the fourth quarter of 2022, compared to $71.2 million during the fourth quarter of 2021. This increase was primarily driven by the advancement of our lead programs and personnel growth to support these programs.
G&A Expenses: General and administrative expenses increased by $1.5 million to $23.6 million during the fourth quarter of 2022, compared to $22.1 million during the fourth quarter of 2021. This increase was primarily related to an increase in stock-based compensation of $2.6 million, offset in part by a decrease in legal expenses of $0.9 million.
Net Loss: The Company’s net loss was $113.4 million for the fourth quarter of 2022, compared to $81.2 million during the fourth quarter of 2021.
Conference Call to Discuss Fourth Quarter and Full-Year 2022 Results

The Company will discuss these results on a conference call today, Thursday, February 23, 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 February 23, at 12 p.m. ET.

On February 23, 2023 Insmed Incorporated (Nasdaq:INSM), a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases, reported financial results for the fourth quarter and full year ended December 31, 2022 and provided a business update (Press release, Insmed, FEB 23, 2023, View Source [SID1234627615]).

"Insmed had a strong finish to 2022 as we rounded out a year of commercial and clinical execution that set the stage for what I believe will be the most meaningful period in our company’s history," commented Will Lewis, Chair and Chief Executive Officer of Insmed. "As we begin 2023, we are excited to share outputs from across our research and development programs that we hope will demonstrate clear benefit for patients with serious unmet medical needs. We expect that achieving this outcome will bolster the value of our pipeline and potentially enable us to grow from addressing tens of thousands of patients to more than a million. For example, with today’s announcement that screening is complete in adult patients in the Phase 3 ASPEN study of brensocatib in bronchiectasis, we are well on our way toward reporting topline results in the second quarter of 2024 and potentially bringing this first-in-disease therapy to patients. Importantly, we are fully capitalized to achieve these milestones and more."

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Recent Pillar Highlights

Pillar 1: ARIKAYCE

ARIKAYCE global revenue grew 30% in 2022 compared with 2021, reflecting strong U.S. performance, the ongoing launch in Japan, and contributions from European markets.

Insmed continues to advance the development of ARIKAYCE in a frontline setting of patients with Mycobacterium avium complex (MAC) lung disease, consisting of the post-marketing confirmatory ARISE and ENCORE trials. Insmed anticipates sharing topline efficacy and safety data from the ARISE study in the third quarter of 2023 and completing enrollment in the ENCORE study by the end of 2023.

Pillar 2: Brensocatib

Patient screening has been completed in adult patients in the Phase 3 ASPEN study, a global, randomized, double-blind, placebo-controlled trial to assess the efficacy, safety, and tolerability of brensocatib in bronchiectasis. Insmed continues to anticipate completing enrollment in this study in the first quarter of 2023 and sharing topline data in the second quarter of 2024.

As previously shared, Insmed plans to initiate a Phase 2 study of brensocatib in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) in mid-2023. Subject to U.S. Food and Drug Administration input, the Company anticipates that the trial will enroll approximately 270 patients randomized to either 10 mg brensocatib, 40 mg brensocatib, or placebo over a 24-week treatment period, with a primary endpoint of change in daily sinus total symptom score.

1
Pillar 3: TPIP

Insmed is currently enrolling two Phase 2 studies of treprostinil palmitil inhalation powder (TPIP), one in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD) and the other in patients with pulmonary arterial hypertension (PAH).

The Company anticipates sharing interim, blinded dose titration and safety and tolerability data from both the PH-ILD and PAH studies in the second half of 2023, pending the rate of enrollment. Topline results from the PH-ILD study are on track to be shared in the first half of 2024.

Pillar 4: Early-Stage Research

Insmed plans to provide an update on its early-stage research portfolio, which encompasses gene therapy, artificial intelligence-driven protein engineering, and protein manufacturing, during an event on May 8, 2023. The event will take place in person in New York and will be webcast live. The Company will offer a deep dive into the various platforms comprising its research engine and an introduction to the experts leading these teams.

As previously shared, Insmed anticipates having at least six investigational new drug (IND) applications filed or Phase 1 studies underway from this portfolio by the end of 2025. The first IND is expected to be filed prior to the May 8 event.

Insmed anticipates sharing clinical data from a few of the earliest patients in a Phase 1/2 gene therapy study in a musculoskeletal disease in the first half of 2024.

Fourth Quarter and Full-Year 2022 Financial Results

Total revenue for the fourth quarter ended December 31, 2022, was $59.3 million, compared to total revenue of $56.1 million for the fourth quarter of 2021. Total revenue for the full year 2022 was $245.4 million, compared to total revenue of $188.5 million for the full year 2021.

Total revenue for the full year 2022 comprised ARIKAYCE net sales of $186.0 million in the U.S., $56.5 million in Japan, and $2.9 million in Europe and rest of world. In the fourth quarter of 2022, Insmed reached an agreement with the French authorities on a final reimbursement price for the temporary authorization for use (Autorisation Temporaire d’Utilisation) program, which resulted in a change in estimate that reduced revenue by approximately $7.5 million in the fourth quarter of 2022, of which $5.8 million related to periods prior to 2022.

Cost of product revenues (excluding amortization of intangibles) was $13.1 million for the fourth quarter of 2022, compared to $13.3 million for the fourth quarter of 2021. For the full year 2022, cost of product revenues (excluding amortization of intangibles) was $55.1 million compared to $44.2 million in 2021.

Research and development (R&D) expenses were $124.8 million for the fourth quarter of 2022, compared to $76.4 million for the fourth quarter of 2021. For the full year 2022, R&D expenses were $397.5 million compared to $272.7 million in 2021.

Selling, general and administrative (SG&A) expenses for the fourth quarter of 2022 were $73.5 million, compared to $65.3 million for the fourth quarter of 2021. For the full year 2022, SG&A expenses were $265.8 million, compared to $234.3 million in 2021.

For the fourth quarter of 2022, Insmed reported a net loss of $160.1 million, or $1.21 per share, compared to a net loss of $113.0 million, or $0.95 per share, for the fourth quarter of 2021. For the full year 2022, Insmed reported a net loss of $481.5 million, or $3.91 per share, compared to a net loss of $434.7 million, or $3.88 per share, in 2021.

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Balance Sheet, Financial Guidance, and Planned Investments

As of December 31, 2022, Insmed had cash, cash equivalents, and marketable securities of $1.15 billion.

The Company’s total operating expenses for the fourth quarter of 2022 were $210.8 million and for the full year 2022 were $702.7 million.

Insmed continues to expect full-year 2023 global revenues for ARIKAYCE to be between $285 million and $300 million.

In 2023, Insmed anticipates that over 80% of total expenditures will be on its mid-to-late stage and commercial programs (ARIKAYCE, brensocatib, and TPIP), and that less than 20% of overall spend will be on its early-stage research programs, reflecting the Company’s historical approach to spending.

The Company plans to invest in the following key activities in 2023:

(i)
commercialization and expansion of ARIKAYCE globally;

(ii)
advancement of brensocatib, including the Phase 3 ASPEN study in patients with bronchiectasis and commercial launch readiness activities, as well as development across additional neutrophil-mediated diseases;

(iii)
advancement of the confirmatory, frontline clinical trial program for ARIKAYCE (ARISE and ENCORE); and

(iv)
advancement of its earlier-stage pipeline, including the Phase 2 clinical development programs for TPIP and development of its early-stage research platforms.

Conference Call

Insmed will host a conference call beginning today at 8:30 AM Eastern Time. Shareholders and other interested parties may participate in the conference call by dialing (844) 200-6205 (U.S.) or (929) 526-1599 (international) and referencing access code 397951. The call will also be webcast live on the company’s website at www.insmed.com.

A replay of the conference call will be accessible approximately 30 minutes after its completion through March 25, 2023, by dialing (866) 813-9403 (U.S.) or (+44) 204-525-0658 (international) and referencing access code 828224. A webcast of the call will also be archived for 90 days under the Investor Relations section of the company’s website at www.insmed.com.

On February 23, 2023 Immedica’s partner Actinium Pharmaceuticals Inc. has reported results for the primary and secondary endpoints from its pivotal phase 3 SIERRA trial of Iomab-B in patients aged 55 and above with relapsed or refractory acute myeloid leukemia (r/r AML) with active disease (Press release, Immedica Pharma, FEB 23, 2023, View Source [SID1234627614]).

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The SIERRA trial met its primary endpoint of superior durable Complete Remission (dCR = CR or CRp (CR with incomplete platelet recovery) lasting ≥6 months after initial CR/CRp following hematopoietic stem cell transplantation HSCT) with a high degree of statistical significance (p<0.0001). The median overall survival (OS) was 6.4 months for Iomab-B and 3.2 months for the physician´s choice of conventional care arm. More importantly, of the 13 patients (22 %) who achieved dCR on the Iomab-B arm 92% were still alive at 1 year and 60% at 2 years, and hence long-term survivors. Iomab-B enabled access to HSCT with 100% engraftment in all patients receiving a therapeutic dose of Iomab-B. Only 14 of the 77 patients randomized to the conventional care arm achieved a CR on physician’s choice of standard therapy and could proceed to HSCT. None of them had a CR duration of ≥6 months (dCR). Iomab-B was well tolerated compared to conventional care.

Results from the SIERRA trial were presented at the Tandem Meetings: Transplantation & Cellular Therapy Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood & Marrow Transplant Research (CIBMTR). The full abstract is found here: View Source

In April 2022, Immedica and Actinium Pharmaceuticals, Inc. entered a license and supply agreement for Iomab-B, where Immedica has the commercial rights in Europe, the Middle East, and North Africa.

Anders Edvell, CEO of Immedica commented: "We are very encouraged by these results. Iomab-B has the potential to significantly improve the outcomes in a patient population that is underserved by current therapies. We look forward to continuing our collaboration with Actinium to make Iomab-B available for patients in our territories".

SIERRA trial results

The SIERRA trial is a prospective, randomized, controlled phase 3 study comparing Iomab-B to physician’s choice of conventional therapy to patients ≥55 years of age with relapsed or refractory acute myeloid leukemia with active disease, a group of patients with dismal prognosis and few effective therapeutic options. Primary endpoint was the rate of dCR (≥ 6 months). Patients not achieving CR with conventional care could crossover (CO) to Iomab-B-based conditioning followed by HSCT. Forty patients from the conventional care arm actually crossed over. The outcome for CO patients receiving Iomab-B was similar to what was seen in the group randomized to Iomab-B.

SIERRA was conducted at 24 of the leading HSCT centers in the United States and Canada. SIERRA enrolled older, heavily pre-treated patients with active disease and high-risk characteristics who would not be offered HSCT in standard practice outside of a clinical trial and therefore have dismal survival outcomes of two to three months.

HSCT access and engraftment:

All patients (N=66) receiving the therapeutic dose of Iomab-B were able to access HSCT with 100% engraftment. Only 14 patients in the conventional care arm did eventually achieve a CR and could proceed to HSCT. The time from randomization to HSCT was more than doubled for these patients compared to patients transplanted after Iomab-B (median 29 vs. 66.5 days)

Primary endpoint – dCR:

Iomab-B met the primary endpoint of dCR, i.e., a CR (or CRp) with a duration of at least 6 months following initial CR after HSCT, with a high degree of statistical significance (p<0.0001)
22% of patients (13/59) in the per protocol analysis achieved dCR in the Iomab-B arm compared to 0% of patients on the control arm.
Secondary endpoints – event free survival and overall survival:

Iomab-B demonstrated significant improvement in EFS with a Hazard Ratio = 0.22, p<0.0001, which means Iomab-B reduced the probability of an event by 78%. Iomab-B numerically doubled the median overall OS compared to patients who were treated with conventional care without crossover (6.4 months vs 3.2 months).
A high percentage of patients achieving dCR after Iomab-B are long term survivors: 92% and 60% were still alive 1 and 2 years after initial CR respectively.
The median OS in the CO arm was 7.1 months.
Safety information:

Iomab-B was well tolerated compared to conventional care.
The incidence of sepsis was four times lower in the Iomab-B arm compared to patients undergoing HSCT in the control arm (6.1% vs 28.6%).

About Iomab-B
Iomab-B is an anti-CD-45 monoclonal antibody conjugated to the radioisotope 131I. CD45 is widely expressed on leukemia and immune cells including bone marrow progenitor stems cells. The radiation emitted from Iomab-B kills both the cells that the antibody binds to, and also the neighboring cells thereby delivering targeted radiation directly to leukemic cells and white blood cells in the myeloid tissue ablating the bone marrow while sparing healthy organs.

Iomab-B is a first-in-class targeted radiotherapy intended to improve patient access to potentially curative HSCT. Multiple studies have demonstrated increased survival in patients receiving HSCT, however, an overwhelming majority of patients with r/r AML do not receive HSCT as current approaches do not produce a remission, which is needed to advance to HSCT, or are too toxic.

Actinium intends to submit a Biologics License Application (BLA) seeking approval for Iomab-B in 2023 to address patients age 55+ with r/r AML with active disease. Iomab-B has been granted Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) and has patent protection into 2037. Iomab-B has also been granted Orphan Drug Designation by the European Medicines Agency (EMA) and Immedica will now start to prepare marketing approval applications relevant for the European territory.

On February 23, 2023 MEI Pharma, Inc. (Nasdaq: MEIP) ("MEI"), a clinical-stage pharmaceutical company focused on advancing new therapies for cancer, and Infinity Pharmaceuticals, Inc. (Nasdaq: INFI) ("Infinity"), a clinical-stage biotechnology company developing eganelisib, a first-in-class, oral, immuno-oncology macrophage reprogramming drug candidate, reported that the companies entered into a definitive merger agreement for an all-stock transaction forming a company combining the expertise and resources of MEI and Infinity to advance a robust pipeline of three clinical-stage oncology drug candidates (Press release, Infinity Pharmaceuticals, FEB 23, 2023, View Source [SID1234627613]). All three clinical-stage development programs have the potential, in combination with current therapies, to overcome known resistance mechanisms and meaningfully improve patient outcomes.

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The combined company’s clinical-stage oncology development pipeline consists of three differentiated programs:

Eganelisib, an oral immuno-oncology macrophage reprogramming product candidate, which is planned to be evaluated in combination with the PD-1 targeted checkpoint inhibitor pembrolizumab (KEYTRUDA) in patients with head and neck squamous cell carcinoma (HNSCC);
Voruciclib, an oral CDK9 inhibitor, currently being studied in combination with venetoclax (VENCLEXTA) in patients with hematologic malignancies; and
ME-344, a novel tumor selective mitochondrial inhibitor targeting the OXPHOS pathway, to be evaluated in combination with bevacizumab (AVASTIN) in patients with relapsed colorectal cancer.
"We are very excited to enter into this agreement with Infinity given the strength of a combined organization that builds on each company’s potential. The combined organization will have three differentiated clinical-stage oncology assets, expected funding into mid-2025 to reach clinical data in all three programs, and a team with extensive oncology clinical development expertise. I believe these ingredients place the merged organization in a strong position to create value for all our stakeholders," said Daniel Gold, Ph.D., President and Chief Executive Officer of MEI Pharma. "The new company’s lead program, eganelisib, has already been tested in over 350 patients with demonstrated clinical activity in multiple settings, including in combination therapy with immune checkpoint inhibitors. Along with voruciclib and ME 344, this gives us three promising clinical-stage programs that we believe have significant potential to deliver improved therapeutic options for patients."

"With this planned merger, we are creating a company that is well capitalized to advance a differentiated clinical-stage therapeutic development pipeline leveraging an experienced drug development and leadership team," said Adelene Perkins, Chief Executive Officer and Chair of Infinity. "With data supporting multiple potential development paths for eganelisib, we have prioritized head and neck cancer based on our ability to leverage encouraging progression free survival data from this patient population in MARIO-1. Unfortunately, head and neck cancer remains an area of high unmet medical need with a relatively short PFS and overall survival in patients treated with checkpoint inhibitor monotherapy. Because of this, we prioritized the initiation of a randomized, controlled Phase 2 clinical study combining eganelisib with pembrolizumab in head and neck cancer patients which is intended to demonstrate improved clinical benefit."

"I am looking forward to leading the combined company which, beyond the promising clinical-stage pipeline, leverages the capabilities and resources of two organizations sharing a commitment to developing new oncology therapeutics. The combined company is built around extensive small molecule development experience based on solid science and backed by promising data," said David Urso, J.D., Chief Operating Officer and General Counsel of MEI Pharma, and the Chief Executive Officer of the combined company upon closing of the merger. "At closing, the combined company is projected to have a strong balance sheet of approximately $100 million which is expected to fund planned studies for our clinical candidates through mid-2025 with the potential to deliver near and long-term value for patients and shareholders."

About the Combined Clinical Pipeline Drug Candidates

The combined company’s pipeline includes three differentiated, clinical-stage, small molecule oncology therapeutic candidates:

Eganelisib: A potential first-in-class, oral, once-daily, immuno-oncology development candidate that selectively inhibits phosphoinositide-3-kinase gamma. Eganelisib has demonstrated encouraging clinical results and tolerability across a broad range of solid tumors in over 350 patients, including head and neck squamous cell carcinoma (HNSCC), metastatic triple-negative breast cancer (mTNBC), as well as urothelial, ovarian and melanoma cancers. The combined company plans to initiate in Q3 2023, subject to U.S. Food and Drug Administration review, a global, randomized, controlled Phase 2 clinical trial of eganelisib plus pembrolizumab vs pembrolizumab for the potential treatment of first line relapsed/metastatic head and neck squamous cell carcinoma. The primary endpoint of the Phase 2 study will be overall survival. In the second half of 2024 we plan to have initial data on safety and progression free survival.
Voruciclib: An orally administered Cyclin-Dependent Kinase 9 (CDK9) inhibitor being clinically investigated for hematological malignancies. CDK9 has important functions in cell cycle regulation, including the modulation of two therapeutic targets in cancer: myeloid leukemia cell differentiation protein (MCL1) and the MYC proto-oncogene protein, which regulate cell proliferation and growth. Voruciclib is currently being evaluated in a Phase 1b trial exploring dose and schedule in patients with acute myeloid leukemia (AML) and B-cell malignancies as a single-agent and in combination with venetoclax. The ongoing Phase 1b trial is expected to report initial results from the combination regimen around the end of 2023.
ME-344: A novel, parenteral, tumor selective mitochondrial inhibitor drug candidate targeting the OXPHOS pathway involved in the production of adenosine. Clinical investigation of ME-344 is focused on use in combination with the VEGF inhibitor bevacizumab (Avastin). Data reported from an investigator-initiated, multi-center, randomized study of ME-344 in combination with the VEGF inhibitor bevacizumab (Avastin) demonstrated biologic activity supporting further clinical investigation. Initiation of a Phase 1b trial is planned to evaluate ME-344 plus bevacizumab in patients with relapsed colorectal cancer in the first half of 2023. Data from the Phase 1b trial to support opening enrollment in an expansion cohort are expected to be reported around the end of 2023.
About the Proposed Merger

Under the terms of the merger agreement, Infinity will become a wholly owned subsidiary of MEI Pharma. Pursuant to an exchange ratio set forth in the merger agreement, the pre-merger MEI Pharma shareholders are expected to own approximately 58.0% and pre-merger Infinity shareholders are expected to own approximately 42.0% of the outstanding equity of the combined company immediately following the merger.

Subject to shareholder approval and the subsequent closing of the merger, the combined company is expected to be renamed and trade on the Nasdaq Stock Market. The combined company would be headquartered in San Diego, California and led by a team with extensive industry and oncology drug development expertise, including David Urso, Chief Executive Officer, Robert Ilaria, Jr., M.D., Chief Medical Officer, and Stéphane Peluso, Ph.D., Chief Scientific Officer. Daniel Gold, Ph.D., and Adelene Perkins, the current chief executive officers of MEI and Infinity, respectively, would serve on the Board of Directors of the combined company. The Board of Directors is expected to be composed of eight members, consisting of Mr. Norman C. Selby, currently Infinity’s Lead Independent Director, who will Chair the Board, Mr. Urso, Dr. Gold, Ms. Perkins, two additional members designated by MEI Pharma, one additional member designated by Infinity and one member mutually agreed upon by MEI Pharma and Infinity.

The merger agreement has been approved by the Boards of Directors of both companies. The merger is expected to close in mid-2023, subject to approvals by MEI Pharma and Infinity shareholders, respectively, and other customary closing conditions.

Torreya Capital, LLC is serving as financial advisor to MEI Pharma, and Morgan, Lewis & Bockius LLP is serving as legal counsel to MEI Pharma. Aquilo Partners, L.P. is serving as financial advisor to Infinity, and WilmerHale is serving as legal counsel to Infinity.

Conference Call and Webcast Information

MEI Pharma and Infinity Pharmaceuticals will host a conference call and webcast today at 8:00 a.m. ET to discuss the merger. To access the live call, please dial 1-833-974-2378 (United States) or 1-412-317-5771 (International). Please ask to join the MEI and Infinity merger conference call.

The conference call will also be webcast live here, as well as from the Events Calendar page in the Investors section of MEI Pharma’s website at www.meipharma.com and the Events & Presentations page in the Investors/Media section of Infinity’s website at www.infi.com. All participants are encouraged to join 10 minutes prior to the start time. An archived version of the webcast will be available on each company’s website for 30 days following the event.

On February 23, 2023 IN8bio, a clinical-stage biopharmaceutical company discovering and developing innovative gamma-delta T cell therapies, reported the ability of its novel non-signaling gamma-delta CAR-T platform (nsCAR) to selectively target leukemic cells while preserving healthy B cells (Press release, In8bio, FEB 23, 2023, View Source [SID1234627612]). The findings were presented by Dr. Lawrence Lamb, IN8bio’s Chief Scientific Officer, during a Plenary session titled "Leveraging the Nexus of the Immune System with Gamma-Delta CAR-T Cells" at the 6th CAR-TCR Summit Europe on February 23rd.

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The current generation of CAR-T technology eliminates the target antigen regardless of whether it is expressed on tumor or healthy tissues. However, IN8bio’s nsCAR platform uses the innate immune recognition of gamma-delta T cells to distinguish between tumor and healthy tissue, offering a targeted but potentially less toxic approach. In a 48-hour in vitro cytotoxicity experiment, the nsCAR platform demonstrated a greater than 15x difference in killing between leukemic cells and healthy B cells (E:T=2:1, 79.7% versus 5.2%) when both express the CD19 target antigen.

The nsCAR platform is also engineered to express the cytokine interleukin-15 (IL-15) to enhance cellular persistence and the ability to target and kill tumor cells over time. The platform has the potential to broaden the utilization of CAR technology for previously "undruggable" solid and liquid tumor targets.

"This powerful approach could be used in indications such as acute myeloid leukemia (AML) and solid tumor cancers where on-target, off-tumor expression would result in toxicities with significant risks to patients," said Lawrence Lamb, Ph.D., co-founder and Chief Scientific Officer of IN8bio. "While CD19 was a preclinical proof-of-concept, we look forward to advancing the nsCAR platform into solid tumor indications as well as promising targets for AML, such as CD33."

The data presented supports the potential of IN8bio’s nsCAR platform to revolutionize the development of future CAR-T therapies, with the findings demonstrating the ability of the novel approach to distinguish between tumor cells and healthy tissue. The presentation is available on the company’s website at View Source

About INB-300

INB-300, our non-signaling CAR gamma-delta T cell platform, includes several preclinical product candidates combining our expertise in gamma-delta T cells and genetic engineering. These nsCAR constructs lack signaling domains in order to take advantage of the unique properties of gamma-delta T cells to differentiate between healthy and tumor tissues. IN8bio is advancing new nsCAR constructs against multiple targets to treat both solid and liquid tumors.