On August 9, 2022 MannKind Corporation (Nasdaq: MNKD) reported that financial results for the second quarter and first half of 2022 (Press release, Mannkind, AUG 9, 2022, View Source [SID1234617912]).

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"In the second quarter, we achieved multiple milestones that position the Company for growth over the next decade," said Michael Castagna, PharmD, Chief Executive Officer of MannKind Corporation. "Tyvaso DPI was approved by the FDA, which allowed us to recognize manufacturing and royalty revenues for the first time this quarter. We also generated revenue from a newly acquired product, V-Go, that is complementary to our endocrine franchise."

Second Quarter 2022 Results

Total revenues were $18.9 million for the second quarter of 2022, reflecting Afrezza net revenue of $10.6 million, V-Go net revenue of $2.1 million, collaborations and services revenue of $5.9 million, and royalties of $0.3 million. Afrezza net revenue increased 7% compared to $10.0 million in the second quarter of 2021 as a result of increased price, which included more favorable gross-to-net deductions, and patient demand which was substantially offset by wholesaler inventory ordering patterns that resulted in lower inventory levels for the second quarter of 2022. Collaborations and services revenue decreased $7.4 million compared to the second quarter of 2021 primarily due to the completion of the R&D Services associated with our collaboration with United Therapeutics ("UT") in the second half of 2021. In August 2021, we entered into a commercial supply agreement ("CSA") with UT. Revenue associated with the CSA was deferred until commercial product was manufactured and sold to UT, which occurred in the second quarter of 2022 when $4.7 million of revenue was recognized. The deferred revenue balance associated with the CSA increased by $4.1 million in the second quarter to $29.8 million as of June 30, 2022. The increase in deferred revenue was associated with the production of commercial product not yet sold to UT and services associated with the Tyvaso DPI production capacity expansion.

Afrezza gross profit for the second quarter of 2022 was $7.3 million compared to $5.6 million in the same period of 2021, an increase of $1.7 million, or 31%, which was driven by an increase in Afrezza sales and a decrease in cost of goods sold. Afrezza’s cost of goods sold decreased by $1.0 million, or 24%, compared to the same period in 2021, primarily attributable to a $2.0 million fee for the amendment of the Insulin Supply Agreement in the prior year period, partially offset by a $1.1 million increase in costs capitalized to inventory due to the timing of production between quarters. Afrezza gross margin in the second quarter of 2022 was 68% compared to 56% for the same period in 2021. V-Go gross profit for the second quarter of 2022 was $0.8 million.

Cost of revenue – collaborations and services in the second quarter of 2022 was $8.3 million compared to $5.5 million for the same period in 2021, an increase of $2.8 million, primarily due to an increase in manufacturing activities for commercial product manufacturing in the second quarter of 2022.

Research and development expenses for the second quarter of 2022 were $4.9 million compared to $2.3 million for the second quarter of 2021. This $2.6 million increase was mainly related to costs incurred for development activities on our product pipeline and the Afrezza pediatrics clinical study (INHALE-1).

Selling, general and administrative expenses for the second quarter of 2022 were $26.0 million compared to $20.0 million for the second quarter of 2021. This $6.0 million increase was primarily attributable to an Afrezza pilot promotional effort aimed at primary care physicians that began in Q4 2021, elimination of the Thyquidity co-promotion (which permitted some expenses associated with the sales force to be recognized as cost of revenue — collaborations and services in 2Q 2021), promotional expenses to support Afrezza growth, V-Go promotional efforts and higher stock-based and other compensation for G&A employees partially offset by lower personnel related costs offset due to Afrezza territory restructuring.

For the second quarter of 2022, the gain on foreign currency translation (for insulin purchase commitments denominated in Euros) was $4.5 million compared to a loss of $0.9 million for the second quarter of 2021. The fluctuation was due to a change in the U.S. dollar to Euro foreign currency exchange rate.

Interest expense on financing liability was $2.4 million for the second quarter of 2022, representing interest incurred on the November 2021 sale and lease-back of our manufacturing facility in Danbury, CT.

Interest expense on notes for the second quarter of 2022 was $6.6 million compared to $3.2 million for the second quarter of 2021. This increase of $3.4 million was primarily due to a $3.9 million increase due to a milestone rights obligation that occurred during the second quarter of 2022 and will be paid in the third quarter. Mann Group converted $10.0 million of debt and capitalized interest into common stock during the second quarter.

The net loss for the second quarter of 2022 was $29.0 million, or $0.11 per share, compared to $35.5 million in the second quarter of 2021, or $0.14 per share. The $6.5 million decrease in the net loss was primarily due to a loss on extinguishment of debt of $22.1 million in the second quarter of 2021 partially offset by lower collaboration and service revenue and an increase in operating expenses.

First half of 2022

Total revenues were $30.9 million for the first half of 2022, reflecting Afrezza net revenue of $20.5 million, V-Go net revenue of $2.1 million, collaborations and services revenue of $8.0 million and royalties of $0.3 million. Afrezza net revenue increased 13% compared to $18.1 million in the first half of 2021 as a result of price, which included more favorable gross-to-net deductions, higher product demand and a more favorable cartridge mix. Collaborations and services revenue for the first half of 2022 decreased $14.6 million compared to the first half ended June 30, 2021, primarily due to the completion in the second half of 2021 of the R&D services associated with our collaboration with United Therapeutics. Revenue associated with the CSA was deferred until commercial product was manufactured and sold to UT, which occurred in the second quarter of 2022 when $5.9 million of revenue was recognized.

Afrezza gross profit for the first half of 2022 was $14.8 million, compared to $9.3 million in the same period of 2021, an increase of $5.5 million, or 58%, which was driven by an increase in Afrezza sales and a decrease in cost of goods sold. Afrezza’s cost of goods sold for the first half of 2022 decreased by $3.1 million, or 35%, compared to the same period in 2021, primarily as a result of a decrease in manufacturing-related spending, a $2.0 million fee for the amendment of the Insulin Supply Agreement in the prior year period plus a decrease in cost of goods sold due to lower manufacturing-related spend for Afrezza as a result of manufacturing a second product. Afrezza gross margin for the first half of 2022 was 72% compared to 52% for the same period in 2021. V-Go gross profit for the second half of 2022 was $0.8 million which was adversely impacted by the purchase price valuation of inventory.

Cost of revenue – collaborations and services for the first half of 2022 was $17.0 compared to $8.8 million in the same period in 2021, an increase of $8.2 million, primarily due to an increase in manufacturing activities leading up to commercial product manufacturing in the second quarter of 2022.

Research and development expenses for the first half ended June 30, of 2022 were $8.4 million compared to $4.8 million for the same period in 2021. This $3.7 million increase primarily attributable to costs incurred for development activities on our product pipeline and the Afrezza pediatrics clinical study (INHALE-1).

Selling, general and administrative expenses for the first half of 2022 were $46.7 million compared to $37.5 million for same period in 2021. This $9.2 million increase was primarily attributable to a pilot promotional effort aimed at primary care physicians that began in Q4 2021, elimination of the Thyquidity co-promotion (which permitted some expenses associated with the sales force to be recognized as cost of revenue — collaborations and services in 2Q 2021), promotional expenses to support Afrezza and V-Go growth and higher stock-based and other compensation for G&A employees.

For the first half of 2022, the gain on foreign currency translation (for insulin purchase commitments denominated in Euros) was $6.5 million compared to $2.9 million for the same period of 2021. The fluctuation was due to a change in the U.S. dollar to Euro foreign currency exchange rate.

Interest expense on financing liability was $4.8 million for the first half of 2022, representing interest incurred on the November 2021 sale and lease-back of our manufacturing facility in Danbury, CT.

Interest expense on notes for the first half of 2022 was $9.4 million compared to $9.6 million in the same period of 2021.

The net loss for the first half of 2022 was $55.0 million, or $0.22 per share, compared to $48.4 million in the same period of 2021, or $0.20 per share. The $6.6 million increase in the net loss was primarily due to total revenues decreasing $9.8 million, selling, general and administrative expenses increasing $9.2 million and cost of revenue – collaboration and services increasing by $8.2 million partially offset by the loss on extinguishment of debt of $22.1 million in the second quarter of 2021.

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 August 9, 2022 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported financial results for the second quarter of 2022 and provided a business update (Press release, Caribou Biosciences, AUG 9, 2022, View Source [SID1234617911]).

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"During the first half of this year, we made significant progress advancing our pipeline of genome-edited allogeneic CAR-T and CAR-NK cell therapies," said Rachel Haurwitz, Ph.D., Caribou’s president and chief executive officer. "We recently presented encouraging initial clinical data at EHA (Free EHA Whitepaper) from our Phase 1 ANTLER trial for CB-010, demonstrating a 100% complete response rate as the best response at dose level 1 in six patients with relapsed or refractory B cell non-Hodgkin lymphoma. Based on the promising initial safety and efficacy data at dose level 1, we are enrolling patients at dose level 2. The ANTLER data have exceeded our expectations and are an important step toward validating our chRDNA genome-editing platform. We are excited to advance our plans for future development of CB-010 and our broader pipeline, including CB-011 for relapsed or refractory multiple myeloma and CB-020, the first solid tumor-targeted program from our CAR-NK platform."

Recent Business Highlights

Pipeline and Technology

ANTLER trial:
Encouraging clinical data from the ANTLER Phase 1 trial of CB-010 in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) were presented in a poster at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress. A 100% complete response (CR) rate (n=6) was observed as best response following a single dose of CB-010 at dose level 1 (40×106 CAR-T cells). CB-010 was generally well tolerated.
Following the EHA (Free EHA Whitepaper) poster presentation, 1 additional patient had their 6-month evaluation, which showed they maintained a CR at 6 months, resulting in an overall 50% 6-month CR rate (n=6) for cohort 1 following a single, starting dose of CB-010.
Additionally, as disclosed concurrently with the EHA (Free EHA Whitepaper) poster, the first patient treated with CB-010 maintained a CR at 12 months.
Based on the promising initial safety data and response rate at dose level 1, the ANTLER trial is currently enrolling patients at dose level 2 (80×106 CAR-T cells) and the company plans to share additional cohort 1 ANTLER data by YE 2022.
chRDNA technology:
Presentation of data on Caribou’s CRISPR hybrid RNA-DNA (chRDNA) technology at the 25th Annual Meeting of the American Society for Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper). The preclinical studies highlighted the mechanism underlying the superior specificity of Caribou’s chRDNA guides for genome editing of primary human T cells.
Corporate

In May 2022, Caribou appointed David Johnson to the board of directors. Mr. Johnson, who currently serves as chief commercial officer at Global Blood Therapeutics, is a seasoned executive with 30 years of commercial and operational experience in the biopharmaceutical industry and has an impressive record of successfully building commercial infrastructure and launching new medicines for patients. Previously, Mr. Johnson worked at Gilead Sciences, Inc. for 15 years and at GlaxoSmithKline for 11 years.
Caribou recently hired several professionals with significant biotechnology and pharmaceutical industry experience:
Tonia Nesheiwat, Pharm.D., vice president of medical affairs
Daniel Poon, vice president of operations and information technology
Socorro Portella, M.D., vice president of clinical development
Saeid Yazdani, vice president of portfolio management
In July 2022, Caribou joined the American Society for Transplantation and Cellular Therapy (ASTCT) Corporate Council to engage in joint problem-solving and collaborative opportunities that will advance the cause and culture of blood and marrow transplantation and cellular therapy.
Anticipated Milestones for 2022 and Beyond

CB-010: Caribou plans to share additional data from cohort 1 of the ongoing ANTLER Phase 1 trial for CB-010, an anti-CD19 CAR-T cell therapy for r/r B-NHL, by YE 2022.
CB-011: Caribou expects to submit an IND application for CB-011, an anti-BCMA CAR-T cell therapy for relapsed or refractory multiple myeloma (r/r MM), in Q4 2022.
CB-020: Caribou expects to announce target selection for CB-020, an iPSC-derived CAR-NK cell therapy for solid tumors, in Q4 2022. Additionally, Caribou expects to disclose armoring strategies under development for its CAR-NK cell platform in Q4 2022.
CB-012: Caribou expects to submit an IND application for CB-012, an anti-CLL-1 CAR-T cell therapy for r/r acute myeloid leukemia (AML), in 2023.
Upcoming 2022 Meetings

September 19-22: 7th Annual CAR-TCR Summit
Syed Rizvi, M.D., Caribou’s chief medical officer, to present an encore of initial ANTLER clinical data
Justin Skoble, Ph.D., Caribou’s vice president of technical operations, to present on how Caribou’s chRDNA genome-editing technology is being applied to increase persistence and antitumor activity in preclinical models
In September and October, Caribou management plans to participate in the following investor conferences:
September 7-8: Citi 17th Annual BioPharma Conference 2022
September 12-14: Morgan Stanley 20th Annual Global Healthcare Conference
September 13: H.C. Wainwright 24th Annual Global Investment Conference
September 29-30: Jefferies Cell and Genetic Medicine Summit
October 6: BMO BioPharma Spotlight Series – Gene Editing & Therapy
Second Quarter 2022 Financial Results

Cash, cash equivalents, and marketable securities: Caribou had $366.1 million in cash, cash equivalents, and marketable securities as of June 30, 2022, compared to $413.5 million as of December 31, 2021.

Licensing and collaboration revenue: Revenue from Caribou’s licensing and collaboration agreements was $4.2 million for the three months ended June 30, 2022, compared to $1.5 million for the same period in 2021. The increase was primarily due to an increase in revenue recognized pursuant to the AbbVie collaboration and license agreement.

R&D expenses: Research and development expenses were $22.6 million for the three months ended June 30, 2022, compared to $12.3 million for the same period in 2021. The increase was primarily due to external activities related to the ANTLER Phase 1 clinical trial and contract manufacturing for CB-010 and additional product candidates; other research and development expenses to advance IND-enabling studies for CB-011 and preclinical research for additional programs; personnel-related expenses, including stock-based compensation, attributable to increased headcount; and facility expenses; partially offset by a decrease in expenses relating to licensing, sublicensing revenue, and milestones.

G&A expenses: General and administrative expenses were $10.0 million for the three months ended June 30, 2022, compared to $5.1 million for the same period in 2021. The increase was primarily due to personnel-related expenses, including stock-based compensation, attributable to increased headcount; facilities and other expenses; and legal, accounting, insurance, and other expenses associated with operating as a public company; partially offset by a decrease in patent cost reimbursements.

Net loss: Caribou reported a net loss of $26.7 million for the three months ended June 30, 2022, compared to $14.3 million for the same period in 2021.

About Caribou’s Novel Next-Generation CRISPR Platform
CRISPR genome editing uses easily designed, modular biological tools to make DNA changes in living cells. There are two basic components of Class 2 CRISPR systems: the nuclease protein that cuts DNA and the RNA molecule(s) that guide the nuclease to generate a site-specific, double-stranded break, leading to an edit at the targeted genomic site. CRISPR systems are capable of editing unintended genomic sites, known as off-target editing, which may lead to harmful effects on cellular function and phenotype. In response to this challenge, Caribou has developed CRISPR hybrid RNA-DNA guides (chRDNAs; pronounced "chardonnays") that direct substantially more precise genome editing compared to all-RNA guides. Caribou is deploying the power of its Cas12a chRDNA technology to carry out high efficiency multiple edits, including multiplex gene insertions, to develop CRISPR-edited therapies.

On August 9, 2022 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for RAS-addicted cancers, reported its financial results for the quarter ended June 30, 2022, and provided an update on corporate progress (Press release, Revolution Medicines, AUG 9, 2022, View Source [SID1234617910]).

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"We continue making progress in the development of innovative medicines on behalf of patients with RAS-addicted cancers, highlighted particularly by the advancement into clinical development of the first two drug candidates from our extensive RAS(ON) Inhibitor portfolio," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "We began dosing patients in a Phase 1/1b trial evaluating RMC-6236 in patients with tumors bearing various KRASG12 mutations, and study site activation is underway for a Phase 1/1b trial of RMC-6291 that shortly will begin dosing patients with tumors specifically bearing a KRASG12C mutation. We expect these exciting clinical-stage compounds will be followed by additional groundbreaking RAS(ON) Inhibitor drug candidates from our collection, including RMC-9805, which we believe is the first oral, covalent inhibitor of KRASG12D, the most common RAS variant causing human cancer.

"Additionally, data from Amgen’s CodeBreaK 101c study presented at the International Association for the Study of Lung Cancer (IASLC) demonstrated the combination of RMC-4630 and sotorasib is safe and tolerable and provided encouraging initial evidence of promising and durable clinical activity in patients with non-small cell lung cancer (NSCLC) bearing a KRASG12C mutation. These exploratory findings support our goal of evaluating the potential benefit of combining RMC-4630 with our own RAS(ON) Inhibitors in development. Further, RMC-4630-03, our Phase 2 study evaluating this drug combination, continues enrolling patients with NSCLC bearing the KRASG12C mutation who have not previously received a KRASG12C inhibitor.

"To support our growing pipeline of development-stage programs, Revolution Medicines recently completed an upsized public equity financing, raising gross proceeds of $265 million. These funds extend the company’s operating runway and enable us to continue executing our robust product development strategy to combat RAS-addicted cancers."

Second Quarter 2022 Clinical and Development Highlights

RAS(ON) Inhibitors

RMC-6236 (RASMULTI)

RMC-6236 is an oral RAS(ON) Inhibitor designed to treat patients with cancers driven by a variety of RAS mutations, including KRASG12D, KRASG12V and KRASG12R. Initially being evaluated as monotherapy, it may also be deployed as a RAS Companion Inhibitor in combination with mutant-selective RAS(ON) Inhibitors.

The company dosed the first patient in its Phase 1/1b monotherapy clinical trial of RMC-6236 and continues enrolling patients. The Phase 1/1b trial (NCT05379985) is a multicenter, open-label, dose-escalation and dose-expansion study of RMC-6236 in patients with advanced solid tumors harboring selected KRASG12 mutations, including KRASG12D, KRASG12V and KRASG12R. To the company’s knowledge, RMC-6236 is the first oral, direct RAS inhibitor to be deployed against a tumor harboring the KRASG12D variant. The company anticipates providing evidence of first-in-class single agent activity for RMC-6236 in 2023.
In April 2022, the company delivered an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting demonstrating that RMC-6236 induced significant monotherapy regressions in mouse clinical trials in diverse models of KRASG12-mutant NSCLC, colorectal cancer (CRC), and pancreatic cancer. It further showed that RMC-6236 deployed as a RAS Companion Inhibitor in combination with RMC-6291 demonstrated enhanced anti-tumor activity in KRASG12C NSCLC and CRC models that were refractory to single agent treatments.
RMC-6291 (KRASG12C)

RMC-6291, an oral, selective, covalent inhibitor of KRASG12C(ON) designed to treat patients with cancers driven by the KRASG12C mutant, is the first of the company’s mutant-selective RAS(ON) Inhibitors to enter clinical development.

Study site activation is ongoing under an investigational new drug (IND) application for a Phase 1/1b trial (NCT05462717) of RMC-6291. The trial is a multicenter, open-label, dose-escalation and dose-expansion study of RMC-6291 monotherapy in patients with advanced KRASG12C-mutant solid tumors. The company expects to announce dosing of the first patient in a monotherapy dose-escalation study of this compound in the second half of 2022 and to provide preliminary evidence of superior activity for this compound in 2023.
In April 2022, the company delivered an oral presentation at AACR (Free AACR Whitepaper) showing that RMC-6291 demonstrated superior preclinical efficacy over adagrasib (MRTX849), Mirati’s KRASG12C inhibitor, in a head-to-head mouse clinical trial in models of KRASG12C NSCLC.
RMC-9805 (KRASG12D)

RMC-9805 is an oral, selective, covalent inhibitor of KRASG12D(ON), the most common driver of RAS-addicted human cancers, predominantly among patients with CRC, pancreatic cancer or NSCLC. The company believes RMC-9805 is the first oral, covalent inhibitor of KRASG12D.

The company expects to announce dosing of the first patient in a monotherapy dose-escalation study of RMC-9805 in mid-2023.
In April 2022, the company delivered an oral presentation at AACR (Free AACR Whitepaper) demonstrating that RMC-9805 produced profound and durable tumor regressions, including complete regressions, in diverse preclinical models of KRASG12D CRC and pancreatic cancer.
RMC-8839 (KRASG13C)

RMC-8839 is an oral, selective, covalent inhibitor of KRASG13C(ON). The company believes RMC-8839 is the first compound to directly inhibit KRASG13C, an important therapeutic target primarily for NSCLC and select CRC patients unserved by a targeted RAS inhibitor.

For 2022 and 2023 the company currently intends to concentrate its development resources on its three most advanced RAS(ON) Inhibitors (RMC-6236, RMC-6291 and RMC-9805) and two RAS Companion Inhibitors that are in the clinic (RMC-4630 and RMC-5552) and therefore expects to determine the timing for announcement of initiating clinical evaluation of RMC-8839 at a future date.
In April 2022, the company delivered an oral presentation at AACR (Free AACR Whitepaper) demonstrating that RMC-8839 induced profound and durable tumor regressions in models of KRASG13C NSCLC. The results also showed that normal RAS proteins contribute to oncogenic signaling in KRASG13C tumor lines, providing the rationale to pursue combination strategies featuring RMC-8839 and RMC-4630, the company’s SHP2 inhibitor capable of inhibiting normal RAS.
RAS Innovation Engine

The company is leveraging its innovative tri-complex inhibitor platform and advanced cancer discovery capabilities to identify additional oral RAS(ON) Inhibitors to target RAS variants driving RAS-addicted cancers that are unserved by a targeted RAS inhibitor.

The company is conducting multiple pipeline expansion programs focused on RAS mutation hotspots G12 (e.g., G12V and G12R), G13 (e.g., G13D) and Q61.
The company expects to nominate a fifth RAS(ON) Inhibitor development candidate in the second half of 2022.
RAS Companion Inhibitors

RMC-4630 (SHP2)

RMC-4630 is a clinical-stage oral inhibitor of SHP2, which contributes to tumor survival and growth in many RAS-addicted cancers. RMC-4630 (also known as SAR442720) continues development under the company’s global SHP2 development and commercialization partnership with Sanofi.

RMC-4630 and KRASG12C Inhibitor Lumakras (sotorasib)

CodeBreaK 101c: Amgen recently reported preliminary results from its CodeBreaK 101c trial, an exploratory Phase 1b study evaluating the combination of RMC-4630 with the KRASG12C inhibitor sotorasib in patients with advanced KRASG12C-mutated solid tumors, at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer. These results demonstrated that the combination was safe and tolerable, and showed promising early clinical activity in NSCLC patients with KRASG12C mutations, particularly in patients who were KRASG12C inhibitor-naïve.
RMC-4630-03: Revolution Medicines continues enrolling patients in its global Phase 2 trial RMC-4630-03 (NCT05054725), a Phase 2 multicenter, open-label study of RMC-4630 in combination with sotorasib for patients with NSCLC with a KRASG12C mutation who have failed prior standard therapy and who have not previously been treated with a KRASG12C inhibitor. The company is sponsoring the RMC-4630-03 study under its global SHP2 partnership with Sanofi and conducting the trial in collaboration with Amgen, which is supplying sotorasib to trial sites globally. Revolution Medicines currently expects to provide topline data from this study in 2023.
RMC-4630 and KRASG12C Inhibitor adagrasib

Sanofi is recruiting patients in a Phase 1/2 dose escalation and expansion study under its SHP2 partnership with Revolution Medicines, and in collaboration with Mirati. The study will evaluate RMC-4630 in combination with adagrasib (MRTX849) in patients with previously treated NSCLC bearing a KRASG12C mutation.
RMC-4630 and PD-1 Inhibitor KEYTRUDA (pembrolizumab)

Sanofi is conducting a Phase 1 trial evaluating RMC-4630 in combination with pembrolizumab, a PD-1 inhibitor, as first-line treatment for patients with PDL-1 positive NSCLC.
RMC-5552 (mTORC1/4EPB1)

RMC-5552 is a first-in-class, bi-steric mTORC1-selective inhibitor designed to suppress phosphorylation and inactivation of 4EBP1 in cancers with hyperactive mTORC1 signaling, including certain RAS-addicted cancers. The company intends to combine RMC-5552 with RAS(ON) Inhibitors in patients with cancers harboring RAS/mTOR pathway co-mutations.

Dose optimization continues in the company’s ongoing Phase 1/1b clinical trial evaluating RMC-5552 monotherapy (NCT04774952). This study is expected to enable combination studies in RAS-addicted cancers. The trial is a multicenter, open-label, dose-escalation study of RMC-5552 monotherapy in patients with refractory solid tumors.
Previously, the company reported preliminary evidence of clinical activity, and reported updated data from this trial at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2022. The data reported at ASCO (Free ASCO Whitepaper) demonstrate marked anti-tumor activity by RMC-5552 in combination with the company’s RAS(ON) Inhibitors in preclinical NSCLC models. The company anticipates disclosing additional evidence of single agent activity in 2023.
Second Quarter 2022 Corporate Highlights

Financing

In July 2022, the company completed an upsized public offering of common stock, raising gross proceeds of $264.5 million before deducting underwriting discounts, commissions and offering expenses. This included the exercise in full by the underwriters of their option to purchase additional shares of common stock. These funds will be used to strengthen the company’s balance sheet and overall financial position to support the continued development and expansion of its product pipeline.

Board Appointments

The company announced two new members to its Board of Directors, Lorence Kim, M.D. and Sushil Patel, Ph.D., who bring their expertise to the Board as the company’s development-stage portfolio continues to mature.

Lorence Kim, M.D. is an accomplished healthcare industry leader who has made significant contributions across the biotechnology and financial industries during his career at Moderna and Goldman Sachs. Dr. Kim brings extensive operational expertise and an extraordinary track record in raising capital for high-growth health care companies.

Sushil Patel, Ph.D. is a seasoned operating executive who brings more than twenty years of experience in the biotech industry, focused on commercialization strategy and execution in U.S. and global oncology markets. During his previous tenure with Genentech, he led lifecycle management of Tecentriq (atezolizumab) in lung cancer and helped lead more than eight product launches across more than twenty different indications.

Second Quarter 2022 Financial Highlights

Cash Position: Cash, cash equivalents and marketable securities were $461.4 million as of June 30, 2022, compared to $577.1 million as of December 31, 2021. The decrease was primarily attributable to net loss for the quarter ended June 30, 2022.

Revenue: Total revenue, consisting of revenue from the company’s collaboration agreement with Sanofi, was $9.1 million for the quarter ended June 30, 2022, compared to $8.7 million for the quarter ended June 30, 2021.

R&D Expenses: Research and development expenses were $61.0 million for the quarter ended June 30, 2022, compared to $45.9 million for the quarter ended June 30, 2021. The increase was primarily due to an increase in research expenses associated with the company’s pre-clinical research portfolio, an increase in personnel-related expenses related to additional headcount, an increase in RMC-6236 expense as a result of commencing clinical trials and an increase in stock-based compensation.

G&A Expenses: General and administrative expenses were $10.2 million for the quarter ended June 30, 2022, compared to $7.3 million for the quarter ended June 30, 2021. The increase was primarily due to an increase in stock-based compensation, an increase in personnel-related expenses related to additional headcount and an increase in legal and accounting fees.

Net Loss: Net loss was $61.2 million for the quarter ended June 30, 2022, compared to net loss of $44.3 million for the quarter ended June 30, 2021.

2022 Financial Guidance

Revolution Medicines is updating its projected full year 2022 GAAP net loss to be between $260 million and $280 million, including estimated non-cash stock-based compensation expense of $30 million to $35 million. With current cash, cash equivalents and marketable securities, including proceeds from the July public offering, the company projects it can fund planned operations through 2024.

Conference Call and Webcast

Revolution Medicines will host a conference call and webcast this afternoon, August 9, 2022, at 4:30 p.m. Eastern Time (1:30 p.m. Pacific Time).

To listen to the conference call, please dial (800) 715-9871 (U.S. toll free) or (646) 307-1963, provide conference ID: 6539267 and request the Revolution Medicines conference call. To listen to the live webcast, or access the archived webcast, please visit: View Source Following the live webcast, a replay will be available on the company’s website for at least 14 days.

On August 9, 2022 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer, reported financial results for the quarter ended June 30, 2022 (Press release, Allogene, AUG 9, 2022, View Source [SID1234617909]).

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"We feel confident that we could soon initiate the industry’s first Phase 2 pivotal trial for an allogeneic CAR T product, thereby paving the road not just for ALLO-501A, but our entire portfolio," said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. "As the use of autologous CAR T therapy increases, we are seeing a greater need for an off-the-shelf, allogeneic CAR T option. We are keenly aware of the devastating consequences patients face when only a minority are able to access the curative potential of CAR T therapy. Clinicians have been forced into the unfathomable position of needing to choose which of their patients will receive this potentially life-saving therapy. As patients face access bottlenecks, we are determined to transform CAR T therapy from a complex individualized procedure to an off-the-shelf, on demand pharmaceutical product."

Pipeline Updates

CD19 Program

In the coming weeks, the Company expects to receive clearance from the U.S. Food and Drug Administration (FDA) to initiate a potential Phase 2 pivotal clinical trial for ALLO-501A in relapsed/refractory (r/r) large B cell lymphoma (LBCL). This includes meeting Chemistry Manufacturing and Controls (CMC) requirements to use ALLO-501A from its manufacturing facility, Cell Forge 1.

In June, the FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to ALLO-501A in r/r LBCL. RMAT designation was based on data demonstrating the potential of ALLO-501A to address the unmet need for patients who have failed other therapies. Previously presented data support the potential of ALLO-501A to provide a safe and durable alternative to approved autologous CAR T therapies in CAR T naïve patients, including manageable safety with no dose limiting toxicities (DLTs) or graft-vs-host disease (GvHD) and minimal Grade 3 Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), or Grade 3 cytokine release syndrome (CRS). In the Phase 1 ALPHA2 study, nearly all enrolled patients were able to receive therapy with the median time from enrollment to initiation of treatment of two days.

Allogene anticipates providing an update on the Phase 1 portion of the ALPHA and ALPHA2 trials toward the end of 2022. This update will include a few additional patients enrolled in ALPHA2 and will focus on longer-term follow up of patients previously treated in the ALPHA and ALPHA2 trials.

The EXPAND trial is expected to begin in 2022 and is planned to support registration of the lymphodepleting agent ALLO-647. This trial is intended to demonstrate the contribution of ALLO-647 to the lymphodepletion regimen.

BCMA Program

Allogene plans to explore its pivotal study approach and timing for its BCMA program by year end. In parallel, the Company intends to work within the framework afforded by its RMAT designation for ALLO-715 to facilitate FDA interactions and determine the best course forward.

Enrollment continues in the Phase 1 UNIVERSAL trial on ALLO-715 in r/r multiple myeloma (MM). Toward the end of 2022, Allogene intends to provide a clinical update that will focus on the longer-term follow up of patients in UNIVERSAL treated with a single dose of ALLO-715. Allogene has made the decision not to advance ALLO-715 in combination with nirogacestat from SpringWorks Therapeutics into dose expansion cohorts. There was no clear indication that the combination would meaningfully improve the benefit-risk profile of ALLO-715 as a monotherapy. Allogene’s Clinical Trial Collaboration Agreement with SpringWorks is expected to remain in effect until the data from the combination study are fully analyzed.

The IGNITE trial on TurboCAR candidate ALLO-605 continues to enroll patients in the dose escalation portion of this Phase 1 study.

Solid Tumor Programs

ALLO-316, which targets CD70, is the Company’s first AlloCAR T candidate for solid tumors. The ongoing Phase 1 TRAVERSE trial is designed to evaluate the safety, tolerability, anti-tumor efficacy, pharmacokinetics, and pharmacodynamics of ALLO-316 in patients with advanced or metastatic clear cell renal cell carcinoma (RCC).

The FDA previously granted ALLO-316 Fast Track Designation (FTD) based on its potential to address the unmet need for patients with difficult to treat RCC who have failed standard therapies. Metastatic solid tumors have historically been a challenge regardless of treatment modality, and the five-year survival rate for patients with advanced kidney cancer is less than 15%, highlighting the need for innovation.

Corporate Highlights
CF1, Allogene’s commercial scale manufacturing facility located in Newark, California is fully operational and producing GMP material with the intent of supplying ALLO-501A for the planned pivotal study as well as other clinical trials. CF1 is projected to have the ability to manufacture approximately 20,000 ALLO-501A AlloCAR T doses annually at scale. CF1 recently earned a LEED Interior Design and Construction Gold designation from the U.S. Green Building Council (USGBS), a non-profit dedicated to sustainable building design and construction.

In July, Allogene announced the appointment of Stephen L. Mayo, Ph.D., a world-renowned expert in computational protein design, to the company’s Board of Directors. Dr. Mayo is the Bren Professor of Biology and Chemistry and Merkin Institute Professor at the California Institute of Technology in Pasadena, California. Dr. Mayo also serves on the Board of Directors of Merck & Co. and Sarepta Therapeutics, Inc.

Second Quarter Financial Results

Research and development expenses were $57.2 million for the second quarter of 2022, which includes $13.0 million of non-cash stock-based compensation expense.
General and administrative expenses were $19.5 million for the second quarter of 2022, which includes $9.9 million of non-cash stock-based compensation expense.
Net loss for the second quarter of 2022 was $74.8 million, or $0.52 per share, including non-cash stock-based compensation expense of $22.9 million.
The Company had $686 million in cash, cash equivalents, and investments as of June 30, 2022.
Updated 2022 Financial Guidance
While the Company anticipates spending to increase in the second half relative to the first half of 2022, it now expects full year GAAP Operating Expenses to be at the low end of the previous range of $360 million and $390 million. This includes estimated non-cash stock-based compensation expense of $90 million to $100 million and excluding any impact from potential business development activities. Cash burn for 2022 is now expected to be approximately $250 million.

Conference Call and Webcast Details
Allogene will host a live conference call and webcast today at 2:00 p.m. Pacific Time / 5:00 p.m. Eastern Time to discuss financial results and provide a business update. To access the live conference call by telephone, please dial 1 (800) 715-9871 (U.S.) or 1 (646) 307-1963 (International). The conference ID number for the live call is 7832993. The webcast will be made available on the Company’s website at www.allogene.com under the Investors tab in the News and Events section. Following the live audio webcast, a replay will be available on the Company’s website for approximately 30 days.

On August 9, 2022 Bio-Path Holdings, Inc., (NASDAQ: BPTH) a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported that it will host a live conference call and audio webcast on Tuesday, August 16, 2022 at 8:30 a.m. ET to report financial results for the second quarter ended June 30, 2022 and to provide a business overview (Press release, Bio-Path Holdings, AUG 9, 2022, View Source [SID1234617908]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

To access the live conference call, please call (833) 630-1956 (domestic) or (412) 317-1837 (international) at least five minutes prior to the start time. A live audio webcast of the call will also be available on the Presentations section of the Company’s website, www.biopathholdings.com. An archived webcast will be available on the Bio-Path website approximately two hours after the event.