On February 23, 2023 Morphic Therapeutic (Nasdaq: MORF), a biopharmaceutical company developing a new generation of oral integrin therapies for the treatment of serious chronic diseases, reported corporate highlights and financial results for the full year 2022 (Press release, Morphic Therapeutic, FEB 23, 2023, View Source [SID1234627619]).

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2022 and Recent Corporate Highlights

EMERALD phase 2 trials of MORF-057 in ulcerative colitis

•Completed enrollment of the EMERALD-1 open-label phase 2a trial of MORF-057 in patients with moderate to severe ulcerative colitis (UC)
◦Study met target enrollment in the third quarter of 2022
◦EMERALD-1 topline results expected in the second quarter of 2023 including primary endpoint (change in Roberts Histopathological Index (RHI)), key secondary measures including modified mayo clinical score (mMCS), safety and pharmacokinetic data
•Initiated EMERALD-2 phase 2b study of MORF-057 in patients with moderate to severe UC
◦EMERALD-2 is a global phase 2b randomized, double-blind, placebo-controlled trial of MORF-057 in patients with moderate-to-severe ulcerative colitis
◦The primary endpoint of EMERALD-2 is clinical remission rate as measured by mMCS at 12 weeks and is expected to report in the first half of 2025

MORF-057 Preclinical and Phase 1 Studies

•Presented new MORF-057 preclinical and clinical data at European Congress for Crohn’s and Colitis, the United European Gastroenterology Week and the American College of Gastroenterology further supporting the ongoing EMERALD phase 2 trials in UC

Integrin Science and Technology

•Celebrated the publication in the scientific journal Cell by Albert Lin, PhD and Timothy Springer, PhD, describing critical insights into the function of integrins, a central biologic receptor class, based on conformation changes
◦The discovery made by Drs. Lin and Springer led directly to the foundation of Morphic Therapeutic
◦Dr. Springer is the Latham Family Professor at Harvard Medical School and recipient of the 2022 Lasker Prize for his pioneering work with integrins, and a founder, Director, and SAB member of Morphic
◦Dr. Lin is Executive Director of Biology at Morphic and a founder of Morphic

Morphic Operations

•Strengthened the Morphic team across research, regulatory, clinical, and executive functions
◦Key additions in 2022 included: the appointment of Dr Brihad Abhyankar as Vice President, Clinical Operations. Dr. Abhyankar was recently promoted to Senior Vice President, Clinical Development, the appointment of Joanne Gibbons as Senior Vice President of Regulatory Affairs. Ms. Gibbons was recently promoted to Senior Vice President, Regulatory Affairs and Quality

"Morphic executed well against our corporate objectives in 2022 which has positioned us ideally for a strong 2023, a key year in the clinical development of MORF-057, our oral a4b7 inhibitor in phase 2 studies for UC", commented Praveen Tipirneni, Chief Executive Officer of Morphic. "We are looking forward to the EMERALD-1 readout in the second quarter while advancing our earlier stage pipeline across multiple therapeutic areas including pulmonary hypertensive diseases, myelofibrosis, and beyond."

Financial Results for the Full Year 2022

•Net loss for the year ended December 31, 2022, was $59.0 million or $1.55 per share compared to a net loss of $95.5 million or $2.67 per share for the year ended December 31, 2021.
•Revenue was $70.8 million for the year ended December 31, 2022, compared to $19.8 million for the year ended December 31, 2021. The change was primarily due to recognition of revenue due to the conclusion of the AbbVie collaboration and reduction in the scope of the Janssen collaboration.
•Research and development expenses were $102.1 million for the year ended December 31, 2022, as compared to $87.8 million for the year ended December 31, 2021. The increase was primarily attributable to higher manufacturing and development costs along with clinical trial costs to support our lead product candidate MORF-057.
•General and administrative expenses were $32.1 million for the year ended December 31, 2022, compared to $27.8 million for the year ended December 31, 2021. The increase was due to increased headcount and higher professional and consulting costs associated with ongoing business development activities and Morphic operating as a public company.

As of December 31, 2022, Morphic had cash, cash equivalents and marketable securities of $348.2 million, compared to $408.1 million as of December 31, 2021. In 2022, Morphic raised net proceeds of $39.2 million from the use of our At-The Market (ATM) facility through its use on a single day in the second quarter. To date in 2023, Morphic has not issued any stock through its ATM facility. On February 13, 2023, the Company entered into a securities purchase agreement pursuant with existing investors for a private placement where the Company agreed to sell and issue 848,655 shares of its common stock at a price of $35.35 per share and pre-funded warrants to purchase 1,980,198 shares of common stock at a purchase price of $35.3499 for an aggregate net proceeds of approximately $100.0 million. We believe that our cash, cash equivalents and marketable securities of $348.2 million as of December 31, 2022, together with the $100.0 million raised in our private issuance of common stock and pre-funded warrants in February 2023, will enable us to fund our operating expenses and capital expenditure requirements into the second half of 2026.

About MORF-057

Morphic is developing MORF-057 as a selective, oral small molecule inhibitor of the α4β7 integrin for patients with inflammatory bowel disease (IBD). α4β7 has been clinically validated as a target for the treatment of IBD by the success of the approved injectable antibody therapeutic vedolizumab. MORF-057, like vedolizumab, is designed to block the interactions between α4β7 on the surface of lymphocytes and the mucosal endothelial cell ligand MAdCAM-1, substantially reducing lymphocyte migration from the bloodstream into intestinal mucosal tissues and avoiding inflammation that is associated with IBD.

About the EMERALD-1 Study

EMERALD-1 (MORF-057-201) is an open-label multi-center phase 2a trial designed to evaluate the efficacy, safety, and tolerability of MORF-057 in adults with moderate to severe ulcerative colitis. EMERALD-1 has completed enrollment of the main cohort of 30-35 patients who will be treated with 100 mg BID (twice daily) at sites in the United States and Europe. The primary endpoint of the trial is the change in Robarts Histopathology Index (RHI), a validated instrument that measures histological disease activity in ulcerative colitis at 12 weeks compared to baseline. Patients will then continue for an additional 40 weeks of maintenance therapy followed by a 52-week assessment. Secondary and additional outcome measures in the EMERALD-1 study include change in the modified Mayo clinic score, safety, pharmacokinetic parameters and key pharmacodynamic measures including α4β7 receptor occupancy and lymphocyte subset trafficking.

About the EMERALD-2 Study

EMERALD-2 (MORF-057-202) is a global phase 2b randomized, double-blind, placebo-controlled trial of MORF-057 that is currently enrolling patients with moderate-to-severe ulcerative colitis. The primary endpoint of EMERALD-2 is clinical remission rate as measured by the Modified Mayo Clinic Score (mMCS) at 12 weeks. EMERALD-2 will also measure several secondary and exploratory endpoints based on the mMCS as well as histologic, pharmacokinetic and pharmacodynamic measures, and safety parameters. Patients in the EMERALD-2 study will be randomized to receive either 200 mg BID (twice daily) MORF-057, 100 mg BID MORF-057, a QD (once daily) dose of MORF-057, or a placebo dose. Following the 12-week induction phase, all patients will receive MORF-057 for 40 weeks of maintenance dosing. For more information about the EMERALD clinical trials of MORF-057, please click here.

On February 23, 2023 MannKind Corporation (Nasdaq: MNKD) reported financial results for the fourth quarter and full year ended December 31, 2022 (Press release, Mannkind, FEB 23, 2023, View Source [SID1234627618]).

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"For 2022, we recognized almost $100 million in total revenues – an incredible triumph for our entire organization," said Michael Castagna, PharmD, Chief Executive Officer of MannKind Corporation. "With our revenues growing nicely, we are focusing on our product pipeline where our INHALE-1 Phase 3 trial for Afrezza in pediatrics reached 50% enrollment at December 31, 2022 and our inhaled clofazimine will move into an adaptive Phase 2/3 study in the second half of 2023."

Fourth Quarter 2022 Results

Revenue Highlights

For the Three Months Ended

December 31,

2022

2021

$ Change

% Change

Net revenue — Afrezza

$

12,006

$

11,340

$

666

6

%

Net revenue — V-Go

5,434

$

5,434

n/a

Revenue — collaborations and services

9,544

1,175

$

8,369

712

%

Royalties — collaborations

9,075

$

9,075

n/a

Total revenues

$

36,059

$

12,515

$

23,544

188

%

The increase in Afrezza net revenue was mainly a result of higher demand. V-Go was acquired in the second quarter of 2022. The increase in collaborations and services revenue reflected the fact that the manufacture of Tyvaso DPI for commercial sale had not yet commenced in the previous period. Royalties from United Therapeutics ("UT") for Tyvaso DPI continued to grow based on strong patient demand.

Afrezza gross margin in the fourth quarter of 2022 was 92% compared to 62% for the same period in 2021, mainly due to a decrease in cost of goods sold driven by lower inventory write offs, lower cost of production per unit and a higher amount of manufacturing activity in 2022 (which absorbed more cost to inventory). V-Go gross margin was 42% for the fourth quarter of 2022.

Cost of revenue – collaborations and services for the fourth quarter of 2022 was $12.0 million compared to $7.1 million for the same period in 2021, an increase of $4.9 million, primarily due to an increase in manufacturing activities associated with the production of Tyvaso DPI.

Research and development ("R&D") expenses for the fourth quarter of 2022 were $7.2 million compared to $3.9 million for the same period in 2021. This $3.3 million increase was primarily attributed to costs incurred to develop our product pipeline, including the Afrezza pediatrics clinical study (INHALE-1) and MNKD-101 (inhaled clofazimine).

Selling expenses for the fourth quarter of 2022 were $11.6 million compared to $13.5 million for the same period in 2021. This $1.9 million decrease was primarily attributable to the net impact of lower personnel-related costs associated with the first quarter of 2022 Afrezza sales force restructuring, and a pilot promotional effort aimed at primary care physicians that began in the fourth quarter of 2021 and ended in the third quarter of 2022, partially offset by V-Go promotional efforts.

General and administrative ("G&A") expenses for the fourth quarter of 2022 were $10.5 million compared to $9.2 million for the same period in 2021. This $1.3 million increase was primarily attributable to higher stock-based compensation and increased headcount.

Interest expense on financing liability was $2.5 million for the fourth quarter of 2022 and represented interest incurred on the sale lease-back transaction for our manufacturing facility in Danbury, CT, which was entered into in the fourth quarter of 2021.

Interest expense on notes was flat in the fourth quarter of 2022 compared to the same period in 2021 due to fixed interest rates and no changes in debt balances.

Year Ended December 31, 2022

Revenue Highlights

For the Year Ended

December 31,

2022

2021

$ Change

% Change

Net revenue — Afrezza

$

43,316

$

39,168

$

4,148

11

%

Net revenue — V-Go

12,931

—

$

12,931

n/a

Revenue — collaborations and services

27,924

36,274

$

(8,350

)

(23

%)

Royalties — collaborations

15,599

$

15,599

n/a

Total revenues

$

99,770

$

75,442

$

24,328

32

%

Afrezza net revenue increased year-over-year primarily due to higher price (including a more favorable gross-to-net adjustment), higher product demand, and a more favorable cartridge mix. Collaborations and services revenue decreased, primarily due to the completion of the R&D services associated with our collaboration with UT, which was partially offset by revenues associated with the manufacturing of Tyvaso DPI. As of December 31, 2022, $37.9 million of manufacturing revenue associated with Tyvaso DPI remains deferred and will be recognized as commercial product is sold to UT.

Afrezza gross margin for 2022 was 80% compared to 57% for the same period in 2021, driven primarily by a decrease in excess manufacturing capacity costs (as Tyvaso DPI was in commercial production in 2022), a decrease in inventory write offs and an amendment fee associated with our Insulin Supply Agreement in 2021. V-Go gross margin was 43% for 2022.

Cost of revenue – collaborations and services for 2022 was $41.5 million compared to $22.0 million for the same period in 2021, an increase of $19.5 million, primarily due to an increase in manufacturing activities for the production of Tyvaso DPI.

R&D expenses for 2022 were $19.7 million compared to $12.3 million for the prior year. This $7.4 million increase was primarily attributable to costs incurred to develop our product pipeline, including (INHALE-1) and MNKD-101. This $7.4 million increase was primarily attributable to costs incurred to develop our product pipeline, including INHALE-1 and MNKD-101.

Selling expenses for 2022 were $53.8 million compared to $45.5 million for the prior year. This $8.3 million increase was primarily attributable to the primary care pilot program, elimination of the Thyquidity co-promotion (which permitted some expenses associated with the sales force to be recognized as cost of revenue for collaborations and services in the same period of 2021), V-Go promotional efforts after the acquisition in the second quarter of 2022, and partially offset by the net favorable impact of personnel-related costs associated with the Afrezza sales force restructuring in 2022.

G&A expenses for 2022 were $37.7 million compared to $31.9 million for the prior year. This $5.8 million increase was primarily attributable to higher stock-based compensation, increased headcount, and higher professional fees.

Interest expense on the financing liability was $9.8 million for 2022 and represented interest incurred on the sale lease-back transaction for our manufacturing facility in Danbury, CT.

Interest expense on notes was flat for 2022 compared to 2021 due to fixed interest rates and no changes in debt balances.

Cash and cash equivalents and investments as of December 31, 2022 were $172.8 million.

Conference Call

MannKind will host a conference call and presentation webcast to discuss these results today at 5:00 p.m. Eastern Time. Those interested in listening to the conference call live via the Internet may do so by visiting the Company’s website at mannkindcorp.com under Events & Presentations. A replay will be available on MannKind’s website for 14 days.

On February 23, 2023 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported fourth quarter and full year 2022 financial results and provided a corporate update (Press release, Kura Oncology, FEB 23, 2023, View Source [SID1234627617]).

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"We continue to have strong conviction in ziftomenib and its potential to be the best-in-class menin inhibitor," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "The speed with which we have begun enrolling patients with NPM1-mutant acute myeloid leukemia (AML) in our registration-directed trial speaks to our impressive Phase 1 data in this population as well as the significant interest in ziftomenib among investigators. In addition, we believe ziftomenib is well positioned for future combination strategies, with no evidence of drug-induced QTc prolongation, no predicted adverse drug-drug interactions and oral daily dosing that should enable convenient administration with standards of care. We continue to prioritize investment in the program and look forward to sharing further updates as the year progresses, including the presentation of a more mature dataset from our Phase 1 trial of ziftomenib in NPM1-mutant AML patients at a medical meeting in mid-2023."

"Meanwhile, clearance of the IND for KO-2806 marks an important next step for our next-generation farnesyl transferase inhibitor (FTI) program," Dr. Wilson continued. "Our preclinical data is supportive of FTIs in combination with a growing number of targeted therapies, including EGFR inhibitors and PI3 kinase alpha inhibitors as well as tyrosine kinase inhibitors in renal cell carcinoma and KRAS G12C inhibitors in lung cancer, and we look forward to starting our first-in-human trial of KO-2806 in the coming months."

Recent Highlights

Updated clinical data from Phase 1 trial of ziftomenib at ASH (Free ASH Whitepaper) – In December, Kura reported updated data from its Phase 1 trial of ziftomenib, the Company’s potent and selective menin inhibitor, in an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The data highlighted the encouraging safety profile and clinical activity of ziftomenib in patients with relapsed/refractory AML, including a 30% complete response (CR) rate with full count recovery among 20 patients with NPM1-mutant AML treated at the 600 mg dose. Notably, two-thirds of NPM1-mutant AML patients who achieved a CR at 600 mg had IDH and/or FLT3 co-mutations, all of whom had failed prior treatment with IDH and/or FLT3 inhibitors. A median duration of response had not been reached as of the ASH (Free ASH Whitepaper) data cutoff on October 24, 2022.

Recommended Phase 2 dose for ziftomenib in NPM1-mutant AML – In December, Kura also announced that 600 mg once-daily dosing has been designated as the recommended Phase 2 dose and schedule for ziftomenib in NPM1-mutant AML following a positive Type C meeting with the U.S. Food and Drug Administration (FDA). Agreement was also reached on key elements of the Company’s Phase 2 registration-directed trial design.

First patients dosed in registration-directed trial of ziftomenib in NPM1-mutant AML – Earlier this month, Kura announced that multiple patients had been dosed in its Phase 2 registration-directed trial (KOMET-001) of ziftomenib in NPM1-mutant relapsed or refractory AML. The Company expects to enroll a total of 85 patients in the U.S. and Europe. The primary endpoint is CR or CR with partial hematologic recovery (CRh), and key secondary endpoints include duration of response, transfusion independence, safety and tolerability. NPM1-mutant AML accounts for approximately 30% of new AML cases annually and represents a disease of significant unmet need for which no approved targeted therapy exists.

Combination trials to support commercial potential for ziftomenib – Kura is preparing to initiate multiple Phase 1 trials to evaluate ziftomenib in combination with current standards of care in earlier lines of therapy and across multiple patient populations, including NPM1-mutant and KMT2A-rearranged AML. The Company intends to establish a foundation where ziftomenib can be combined safely with various commonly used regimens, such as venetoclax plus azacitidine, FLT3 inhibitors and standard induction cytarabine plus daunorubicin (7+3) chemotherapy, then prioritize those combinations that represent the largest populations and greatest potential commercial value. Kura expects to initiate the first of these trials, KOMET-007, in the first half of 2023.

Preliminary proof of mechanism of tipifarnib plus alpelisib in HNSCC – In October, Kura reported the first demonstration that the combination of tipifarnib and alpelisib can induce a durable clinical response in PIK3CA-dependent head and neck squamous cell carcinoma (HNSCC) at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium. A patient with stage III squamous cell carcinoma of the tonsil with a PIK3CA mutation achieved a durable partial response in the Company’s KURRENT-HN trial and continued on-study for more than 27 weeks as of the data cutoff on September 14, 2022. Treatment-related adverse events in KURRENT-HN are consistent with the known safety profiles of each drug and are manageable, with no dose-limiting toxicities reported to date.

IND for KO-2806, a next-generation farnesyl transferase inhibitor – Last month, Kura announced FDA clearance of its Investigational New Drug (IND) application for KO-2806 for the treatment of advanced solid tumors. KO-2806 is a potent inhibitor of farnesyl transferase designed to improve upon potency, pharmacokinetic and physicochemical properties of earlier FTI drug candidates. The Company intends to evaluate safety, tolerability and preliminary antitumor activity of KO-2806 in a Phase 1 dose-escalation trial (FIT-001) as a monotherapy and in combination with other targeted therapies in adult patients with advanced solid tumors.

$25 million equity investment from Bristol Myers Squibb – In November, Kura sold 1,370,171 shares to Bristol Myers Squibb at a price of $18.25 per share for gross proceeds of $25 million. In connection with the equity investment, Bristol Myers Squibb has appointed a member to Kura’s Global Steering Committee. The equity investment further strengthens the relationship between the two organizations and enables Bristol Myers Squibb, a leader in the discovery and development of transformational cancer treatments, to provide valuable strategic input into Kura’s global development strategy.
Financial Results

Research and development expenses for the fourth quarter of 2022 were $22.7 million, compared to $21.0 million for the fourth quarter of 2021. R&D expenses for the full year 2022 were $92.8 million, compared to $84.7 million for the prior year.

General and administrative expenses for the fourth quarter of 2022 were $12.5 million, compared to $12.1 million for the fourth quarter of 2021. G&A expenses for the full year 2022 were $47.1 million, compared to $46.5 million for the prior year.

Net loss for the fourth quarter of 2022 was $33.1 million, compared to a net loss of $32.7 million for the fourth quarter of 2021. Net loss for the full year 2022 was $135.8 million, compared to a net loss of $130.5 million for the prior year. Net loss for the fourth quarter and full year 2022 included non-cash, share-based compensation expense of $6.8 million and $26.3 million, respectively, compared to $6.4 million and $23.6 million for the same periods in 2021.

Cash, cash equivalents and short-term investments totaled $438.0 million as of December 31, 2022, including the $25 million equity investment from Bristol Myers Squibb and a one-time $10 million draw from a term loan facility with Hercules Capital, compared with $518.0 million as of December 31, 2021. Based on its operating plan, management expects that cash, cash equivalents and short-term investments will fund current operations into the fourth quarter of 2025.
Forecasted Milestones

Dose the first patients in the KOMET-007 combination trial of ziftomenib in the first half of 2023.

Present updated data from the KOMET-001 trial of ziftomenib in NPM1-mutant AML at a medical meeting in mid-2023.

Dose the first patients in the KOMET-008 combination trial of ziftomenib in the second half of 2023.

Determine the optimal biologically active dose in the KURRENT-HN trial of tipifarnib in combination with alpelisib in mid-2023.

Dose the first patients in the FIT-001 dose-escalation trial of KO-2806 in the third quarter of 2023.
Conference Call and Webcast

Kura’s management will host a webcast and conference call at 4:30 p.m. ET / 1:30 p.m. PT today, February 23, 2023, to discuss the financial results for the fourth quarter and full year 2022 and to provide a corporate update. The live call may be accessed by dialing (877) 407-4018 for domestic callers and (201) 689-8471 for international callers and entering the conference ID: 13735896. A live webcast and archive of the call will be available online from the investor relations section of the company website at www.kuraoncology.com.

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.

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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.