On February 24, 2022 Compugen Ltd. (Nasdaq: CGEN, "Compugen", the "Company"), a clinical-stage cancer immunotherapy company and leader in predictive target discovery, reported financial results for the fourth quarter ended December 31, 2021, and full year 2021 and provided an update on recent Company highlights (Press release, Compugen, FEB 24, 2022, View Source [SID1234608957]).

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"Compugen made excellent progress in 2021. As the leader in the DNAM-1 axis we believe that blocking its complementary pathways has the potential to be a game changer in treating inflamed as well as less inflamed tumors, in patients who do not respond to available therapies. I am particularly excited about the translational data we presented across all the regimens with the most potent immune activation in the triple blockade of PVRIG, TIGIT and PD-1, which complements the early signals of anti-tumor activity we reported in our studies. With COM902, we were the first to present early signals of monotherapy anti-tumor activity with an IgG4 anti-TIGIT antibody, with low Fc-effector function. COM902 also avoided depletion of CD8+ T cells, the most effective anti-cancer immune subset, supporting our strategy to develop an antibody with low Fc effector function said," Anat Cohen-Dayag, Ph.D., President and CEO of Compugen. "In 2021 we also presented additional research supporting the differentiation of PVRIG from other immune checkpoints, enhancing our belief that PVRIG may be the missing piece when current immunotherapies have failed, by potentially generating new waves of T cells to infiltrate the tumor microenvironment. I am excited that the totality of results we have presented to date support our DNAM-1 axis hypothesis and set the stage for the next steps for the Company’s clinical program."

Dr. Cohen-Dayag further commented, "I am also pleased that we expanded our collaboration with Bristol Myers Squibb with a $20 million strategic investment and I am happy to see AstraZeneca progressing its TIGIT/PD-1 bispecific, which is derived from our COM902 into the clinic."

Dr. Cohen-Dayag continued, "Looking ahead, this year and next year we will focus on completing clinical study enrollment and delivering meaningful clinical and translational results from the expansion cohorts in our three ongoing combination studies with our two proprietary programs, COM701 and COM902. We expect to report data from fully enrolled cohorts in each of our studies as available starting with the COM701/nivolumab study CRC (MSS) cohort in Q4 2022, and complete enrollment in all cohorts by the end of 2023. The data from these studies will guide our regulatory strategy on a cohort-by-cohort basis."

2022-2023 Expected Milestones:
•
Advancing the enrollment of Phase 1 and Phase 1/2 dose expansion studies to evaluate anti-PVRIG and/or anti-TIGIT antibodies in combination with a PD-1 inhibitor:

o
COM701/PVRIG plus nivolumab

o
COM701/PVRIG plus COM902/TIGIT

o
COM701/PVRIG plus nivolumab and Bristol Myers Squibb’s investigational anti-TIGIT antibody, BMS-986207
•
Reporting data from fully enrolled cohorts
•
Announcing initial clinical data from the Phase 1 and Phase 1/2 programs starting with COM701/nivolumab study CRC/MSS cohort in Q4 2022
•
Completing enrollment of all ongoing studies by end of 2023

Phase 1/Phase 1/2 Dose Expansion Combination Program
Clinical Study
Number of cohorts
Tumor types
Patients per cohort
COM701+ nivolumab
4
Ovarian, Endometrial, Breast, CRC/MSS
20
COM701+ nivolumab + BMS986207
4
Ovarian, Endometrial, HNSCC, PVRL2+ patients
20
COM701 +COM902
3
HNSCC, NSCLC, CRC/MSS
20

2021 Corporate Highlights
•
Completed enrollment as planned and presented data from our Phase 1 studies at major medical meetings

o
ASCO 2021

◾
COM701 monotherapy dose escalation and expansion studies

◾
COM701 + nivolumab dose escalation study

o
SITC 2021

◾
COM902 monotherapy dose escalation

◾
COM701+ nivolumab + BMS986207 dose escalation
•
COM701 as mono, dual, and triple therapy showed early signals of anti-tumor activity with immune activation and a favorable safety profile
•
COM902 showed early signals of anti-tumor activity, was well tolerated and translational data support choice of an IgG4 anti-TIGIT antibody with less effector function than IgG1

•
Initiated enrollment in the Phase 1, Phase 1/2 dose expansion programs (see table above)
•
Expanded the clinical research collaboration agreement with Bristol Myers Squibb with an equity investment of $20 million
•
Received $6 million milestone payment triggered by first patient initiation in AstraZeneca’s Phase 1/2 study of a TIGIT/PD-1 bispecific monoclonal antibody, AZD2939, derived from COM902
•
Expanded research collaboration with Johns Hopkins University for a novel myeloid target discovered by Compugen
•
Published review on biology and potential therapeutic relevance of DNAM-1 axis in cancer immunotherapy in Cancer Discovery, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper)
•
Published preclinical data on the potential of COM902 to enhance anti-tumor immune responses, in Cancer Immunology Immunotherapy
•
Presented research supporting the differentiation of PVRIG from other immune checkpoint inhibitors at the SITC (Free SITC Whitepaper) 2021 Targets for Cancer Immunotherapy seminar series in June, the SITC (Free SITC Whitepaper) in November and translational data from patient biopsies demonstrating immune activation in the TME after treatment with COM701, at the TIGIT Therapies Digital Summit in December

Fourth Quarter and Full Year 2021 Financial Highlights
Cash: As of December 31, 2021, cash, cash related accounts, short-term and long-term bank deposits totaled to approximately $118 million, compared with approximately $124 million as of December 31, 2020. The Company expects its existing cash and cash equivalents and short-term bank deposits, to be sufficient to fund our current level of operations into 2024.

Revenues: Compugen reported no revenue for the fourth quarter of 2021 and a total of $6 million for the year ended December 31, 2021, compared with $2.0 million for each of the comparable periods in 2020. 2021 revenues are related to the milestone payment from AstraZeneca for dosing the first patient in AstraZeneca’s Phase 1/2 study of a TIGIT bispecific monoclonal antibody, derived from COM902.

Cost of revenues: 2021 expenses of approximately $0.7 million are attributed to royalty and milestone payments.

R&D Expenses: Expenses for the fourth quarter and year ended December 31, 2021 were approximately $5.8 million, and approximately $28.7 million, respectively, compared with approximately $8.1 million and approximately $22.8 million for the comparable periods in 2020. The increase in the annual periods is attributed mainly to higher expenses associated with our various clinical studies, manufacturing and related costs, and headcount as the U.S. based clinical team continues to grow to support the expansion of our studies. The decrease in the quarterly period is due to a decrease in manufacturing and related costs.

G&A Expenses: Expenses for the fourth quarter and year ended December 31, 2021 were approximately $2.7 million and approximately $10.9 million, respectively, compared with approximately $2.7 million and approximately $9.8 million for the comparable periods in 2020. The increase in the annual period is mainly due to increased corporate-related expenses.

Net Income/Loss: Net loss for the fourth quarter of 2021 was approximately $8.6 million, or $0.10 per basic and diluted share, compared with a net loss of approximately $8.6 million, or $0.10 per basic and diluted share in the comparable period of 2020. Net loss for the year ended December 31, 2021 was approximately $34.2 million, or $0.41 per basic and diluted share, compared with net loss of approximately $29.7 million, or $0.37 per basic and diluted share in the comparable period of 2020.

Full financial tables are included below.

Conference Call and Webcast Information
The Company will hold a conference call today, February 24, 2022, at 8:30 AM ET to review its fourth quarter and full year 2021 results. To access the conference call by telephone, please dial 1-866-744-5399 from the United States, or +972-3-918-0610 internationally. The call will also be available via live webcast through Compugen’s website, located at the following link. Following the live audio webcast, a replay will be available on the Company’s website.

On February 24, 2022 Cellectis (Euronext Growth: ALCLS – Nasdaq: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported that it will report its financial results for the fourth quarter and year-end 2021 ending December 31, 2021, on Thursday, March 3, 2022, after the close of the US market (Press release, Cellectis, FEB 24, 2022, View Source [SID1234608955]).

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The announcement will be followed by a conference call and live audio webcast on Friday, March 4, 2022, at 8:00 AM EDT / 2:00 PM CET, prior to the open of the US market. The call will include the Company’s fourth quarter results, year-end results, and an update on business activities. Details for the call are as follows:

On February 24, 2022 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported recent company highlights and financial results from the fourth quarter and full year ended December 31, 2021 (Press release, Cardiff Oncology, FEB 24, 2022, View Source [SID1234608954]).

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"Our recent progress has provided additional clinical and external validation of onvansertib, including a Pfizer Breakthrough Growth Initiative collaboration," said Mark Erlander, Ph.D., chief executive officer of Cardiff Oncology. "As the number of evaluable patients in our lead program in KRAS-mutated metastatic colorectal cancer increased from 14 to 48 over the past year, we continued to see consistent objective response rates and median progression-free survival that substantially exceed those from historical control trials. We have also seen responses across multiple KRAS-mutation variants, which differentiates onvansertib from agents designed to target a specific KRAS mutation. We look forward to advancing our mCRC clinical program and moving into a pivotal trial."

Dr. Erlander added, "Alongside our lead program in mCRC, we continue our work to leverage onvansertib in other cancer indications. The addition of Tod Smeal, Ph.D., as our chief scientific officer was an important step towards this goal, and his experience developing targeted cancer therapies is already proving to be an invaluable asset. Looking ahead, we are eager to continue exploring synergistic combinations with onvansertib, which include DNA damaging agents, microtubule inhibitors and epigenetic factors, as we pursue additional indications."

Program highlights for the quarter ended December 31, 2021, and recent business updates include:

KRAS-mutated Metastatic Colorectal Cancer (mCRC) Program:

Announced new data from Phase 1b/2 trial evaluating onvansertib plus FOLFIRI/bevacizumab that continue to show robust objective response rate and progression-free survival

The data were presented on a webcast and conference call hosted by Cardiff Oncology, and a subset were featured in a poster presented by Heinz-Josef Lenz, M.D., FACP, principal investigator, USC Norris Comprehensive Cancer Center, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI). Highlights from the webcast and conference call included:

Efficacy data in evaluable patients:

Among patients treated per protocol at the recommended Phase 2 dose (RP2D; 15 mg/m2) in combination with FOLFIRI/bevacizumab:
12 of 35 (34%) achieved an initial complete response (CR) or partial response (PR)
10 of 35 (29%) achieved a confirmed CR or PR (awaiting confirmatory scan for 1 patient)
Objective response rates of 5-13% observed in historical control trials in similar patient populations treated with various different drug combinations, including the standard-of-care chemotherapy of FOLFIRI with bevacizumab1-4
Patients evaluable for response treated at all dose levels (12 mg/m2, 15 mg/m2, 18 mg/m2)
17 of 48 (35%) achieved an initial CR or PR
13 of 48 (27%) achieved a confirmed CR or PR (awaiting confirmatory scan for 1 patient)
Median progression-free survival (mPFS), biomarker, and safety data:

mPFS has not yet been reached in patients treated per protocol at the RP2D
mPFS across all response-evaluable patients (n = 48) is 9.4 months (95% confidence interval: 7.1 – not yet reached)
mPFS of ~4.5-5.7 months has been reported in trials used as historical controls1-4
Responses (CRs or PRs) were observed across seven different KRAS mutation variants, including the 3 most commonly observed in colorectal cancer (G12D, G12V, G13D)
The combination of onvansertib and FOLFIRI/bevacizumab was shown to be well-tolerated with only 11% (84/788) of reported treatment-emergent adverse events (TEAEs) being G3/G4
Corporate Highlights:

Received a $15 million equity investment from Pfizer as part of the Pfizer Breakthrough Growth Initiative

Pfizer purchased 2.4 million shares of Cardiff Oncology’s common stock at a price of $6.22 per share, which represented a 19% premium compared to the prior closing price. In connection with the equity investment, Adam Schayowitz, Ph.D., MBA, Vice President & Medicine Team Group Lead for Breast Cancer, Colorectal Cancer and Melanoma at Pfizer, will join Cardiff Oncology’s Scientific Advisory Board. Additionally, Cardiff Oncology agreed to grant Pfizer rights of first access to data from its development programs.

Strengthened management team with the appointments of Tod Smeal, Ph.D., as CSO and Charles Monahan, R.Ph., SVP, regulatory affairs

Dr. Smeal has over 20 years of industry experience developing targeted therapies and previously served as CSO of Cancer Biology at Eli Lilly and Company, and director of the Oncology Research Unit of Pfizer. Mr. Monahan is a registered pharmacist with over 20 years of regulatory experience developing drugs and biologics for oncology, infectious diseases, and ocular indications. Prior to joining Cardiff Oncology, he most recently served as the global head of regulatory affairs for Erytech PharmaSA.

Fourth Quarter and Full Year 2021 Financial Results:

As of December 31, 2021, Cardiff Oncology had approximately $141 million in cash, cash equivalents, and short-term investments.

Total operating expenses were approximately $9.6 million for the three months ended December 31, 2021, an increase of $3.0 million from $6.6 million for the same period in 2020. The increase in operating expenses was primarily due to ongoing and new onvansertib clinical development programs and preclinical activities, additional outside services, and recruiting fees.

Research and development expenses increased by approximately $2.6 million to $5.8 million for the three months ended December 31, 2021, from $3.2 million for the same period in 2020. The increase in research and development expenses was primarily due to advancing the onvansertib clinical and preclinical programs and recruitment fees to fill critical research and development positions.

Selling, general and administrative expenses increased by approximately $0.4 million to $3.8 million for the three months ended December 31, 2021, from $3.4 million for the same period in 2020. The increase in selling, general and administrative expenses was primarily due to strategic valuation consulting related to our lead drug candidate onvansertib offset by lower legal expenses.

Net cash used in operating activities for the fourth quarter of 2021 was approximately $7.4 million, an increase of approximately $2.3 million from $5.1 million for the same period in 2020. This increase is primarily due to advancing clinical program activities and outside services and recruiting fees, and net changes in assets and liabilities.

Total operating expenses were approximately $29.2 million for the full year ended December 31, 2021, an increase of $9.8 million from $19.4 million for the full year 2020. The increase in operating expenses was primarily due to advancing existing and new onvansertib clinical development programs and preclinical activities, additional outside services, recruiting fees and stock compensation expense.

Research and development expenses increased by approximately $6.2 million to $17.4 million for the full year ended December 31, 2021, from $11.2 million for the full year 2020. The increase in research and development expenses was primarily due to advancing existing and new preclinical programs and collaborations.

Selling, general and administrative expenses increased by approximately $3.6 million to $11.8 million for the full year ended December 31, 2021, from $8.2 million for the full year 2020. The increase in selling, general and administrative expenses was primarily due to strategic valuation consulting, recruitment fees, and stock-based compensation expense.

Net cash used in operating activities for the full year 2021 was approximately $23.0 million, an increase of approximately $6.7 million from $16.3 million for the full year 2020.

On February 24, 2022 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science to develop a new generation of small-molecule medicines and transform how disease is treated, reported business highlights and financial results for the year ended December 31, 2021 (Press release, C4 Therapeutics, FEB 24, 2022, View Source [SID1234608953]).

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"The progress achieved across our organization in 2021, a year in which we dosed the first patient with our lead program while advancing additional candidates towards the clinic, was instrumental in laying a foundation for C4T’s vision to transform patient care through targeted protein degradation," said Andrew Hirsch, chief executive officer of C4 Therapeutics. "Supported by the strength of our balance sheet and the productivity of our TORPEDO platform, we are well-positioned to advance our pipeline in 2022. We look forward to the AACR (Free AACR Whitepaper) Annual Meeting, where we will share clinical data from Cohort A in our Phase 1/2 trial evaluating CFT7455 in hematologic malignancies, as well as pre-clinical data from three programs that demonstrate differentiation and versatility of our TORPEDO platform. Throughout 2022, we expect to drive our pipeline forward, with plans to initiate first-in-human studies of CFT8634, a BRD9 degrader, and CFT1946, a BRAF V600X degrader."

RECENT HIGHLIGHTS

CFT7455: CFT7455 is a novel degrader targeting IKZF1/3 for the treatment of multiple myeloma (MM) and non-Hodgkin’s lymphomas (NHL), including peripheral T-cell lymphoma and mantle cell lymphoma.

Clinical Data from Cohort A and Pre-Clinical Data Characterizing the Chemical Structure of CFT7455 Accepted for Presentation at AACR (Free AACR Whitepaper): Clinical data from Cohort A, characterizing pharmacokinetic (PK) and pharmacodynamic activity alongside safety and biomarker data, has been accepted for presentation at the AACR (Free AACR Whitepaper) Annual Meeting, hosted April 8-13, 2022. C4T will also present pre-clinical data characterizing the chemical structure of CFT7455 and the resulting improvements in potency and optimized PK properties.

Progressed CFT7455 Phase 1/2 clinical trial: Enrollment in Cohort A is complete. The ongoing Phase 1/2 trial continues to recruit patients in Cohort B1 (single agent CFT7455 in MM) and Cohort C (single agent CFT7455 in NHL).
Presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition: In December 2021, Jesus G. Berdeja, M.D., director, multiple myeloma research at Sarah Cannon Research Institute, presented a trial-in-progress poster for the CFT7455 Phase 1/2 trial.
CFT8634: CFT8634 is a degrader targeting BRD9 for the treatment of synovial sarcoma and SMARCB1-null solid tumors.

Pre-clinical Data Accepted for Presentation at AACR (Free AACR Whitepaper): C4T will present pre-clinical data on the discovery and characterization of CFT8634.
Obtained FDA Clearance of IND Application for CFT8634: In December 2021, the U.S. Food and Drug Administration (FDA) cleared C4T’s investigational new drug (IND) application for CFT8634 and granted approval for C4T to proceed with the proposed Phase 1/2 trial, for which site activation efforts have commenced and the trial remains on track to begin dosing patients in 1H 2022.
Presented at the 4th Annual Targeted Protein Degradation Summit: In October 2021, C4T delivered a presentation describing the multiparameter optimization of a series of BRD9 degraders, which led to the identification of a degrader with a sufficient intravenous PK profile to enable in vivo proof-of-concept studies. This work served as a launching point for further optimization and eventually led to the discovery of CFT8634.
CFT1946: CFT1946 is a mutant-selective degrader of BRAF V600X for the treatment of V600 mutant solid tumors.

Pre-clinical Data Accepted for Presentation at AACR (Free AACR Whitepaper): C4T will present pre-clinical data on the discovery and characterization of CFT1946.
CFT8919: CFT8919 is a potent and selective degrader of EGFR L858R for the treatment of non-small cell lung cancer.

Presented at the 4th Annual Targeted Protein Degradation Summit: In October 2021, C4T delivered an encore presentation of the Company’s June presentation at the Keystone Symposium on targeted protein degradation. The presentation included pre-clinical data demonstrating CFT8919 is active in in vitro and in vivo models of acquired resistance to approved EGFR inhibitors that harbor resistance-causing secondary mutations in EGFR.
KEY UPCOMING MILESTONES

The company plans to achieve the following milestones in 2022:

CFT7455

Present clinical data from Cohort A of ongoing Phase 1/2 trial of CFT7455 at the AACR (Free AACR Whitepaper) Annual Meeting.
Present pre-clinical data characterizing the chemical structure of CFT7455 and the resulting improvements in potency and optimized PK properties at the AACR (Free AACR Whitepaper) Annual Meeting.
Progress CFT7455 Phase 1/2 trial toward identifying a recommended Phase 2 dose for MM and NHL.
CFT8634

Present pre-clinical data on the discovery and characterization of CFT8634 in synovial sarcoma at the AACR (Free AACR Whitepaper) Annual Meeting.
Initiate a Phase 1 trial for CFT8634 in synovial sarcoma and SMARCB1-null solid tumors in 1H 2022.
CFT1946

Present pre-clinical data on the discovery and characterization of CFT1946 in BRAF V600X driven cancers at the AACR (Free AACR Whitepaper) Annual Meeting.
Submit an IND application and initiate a Phase 1 trial of CFT1946 in BRAF V600X-driven cancers including melanoma, colorectal and non-small cell lung cancer in 2H 2022.
CFT8919

Complete IND-enabling activities for CFT8919 by year-end 2022.
UPCOMING INVESTOR EVENTS

C4T will participate in the following upcoming investor conferences:

February 24, 2022 – BMO Biopharma Spotlight Series: Protein Degraders and Other Next Gen Technologies
March 9, 2022 – Cowen & Co. 42nd Annual Health Care Conference
March 16, 2022 – Guggenheim Targeted Protein Degradation Day
March 17, 2022 – Oppenheimer’s 32nd Annual Healthcare Conference
FULL YEAR 2021 FINANCIAL RESULTS

Revenue: Total revenue for the year ended December 31, 2021 was $45.8 million, compared to $33.2 million for the year ended December 31, 2020. Total revenue reflects revenue recognized under collaboration agreements with Roche, Biogen and Calico. The increase in revenue was primarily driven by the recognition of all previously unrecognized consideration allocated to the BRAF program upon the termination of the Roche agreement as related to that target.

Research and Development (R&D) Expense: R&D expense for the year ended December 31, 2021 was $94.7 million, compared to $78.4 million for the year ended December 31, 2020. The increase in R&D expense was primarily attributable to clinical costs incurred during the year, an increase in preclinical costs related to our lead programs, and increased workforce expenses to support our growing clinical development activities.

General and Administrative (G&A) Expense: G&A expense for the year ended December 31, 2021 was $33.3 million, compared to $15.2 million for the year ended December 31, 2020. The increase in G&A expense was primarily attributable to increased workforce expenses from our growing G&A function, and higher professional fees and insurance costs resulting from our transition to a public company in October 2020.

Net Loss and Net Loss per Share: Net loss for the year ended December 31, 2021 was $83.9 million, compared to $66.3 million for the year ended December 31, 2020. Net loss per share for the year ended December 31, 2021 was $1.82, compared to $5.83 for the year ended December 31, 2020. The decrease in net loss per share despite the increase in net loss was driven by a significant increase in the weighted-average shares outstanding from 11,370,328 as of December 31, 2020 to 46,041,733 as of December 31, 2021. This increase in shares outstanding was caused by our initial public offering of 11,040,000 common shares in October 2020 and the resultant conversion of then outstanding shares of redeemable convertible preferred stock into 30,355,379 shares of common stock, together with our issuance of 4,887,500 shares of common stock upon the closing of our follow-on public offering in June 2021.

Cash Position and Financial Guidance: Cash, cash equivalents and marketable securities as of December 31, 2021 were $451.5 million, compared to $371.7 million as of December 31, 2020. The change in cash was primarily driven by net proceeds from our June 2021 follow-on public offering of $169.5 million, offset by expenditures to fund operations. C4T expects that its cash, cash equivalents and marketable securities as of December 31, 2021, together with future payments expected to be received under existing collaboration agreements, will be sufficient to fund planned operating expenses and capital expenditures to the end of 2024.

On February 24, 2022 BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio or the Company), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, reported its financial results for the fourth quarter ended December 31, 2021 and provided an update on the Company’s operations (Press release, BridgeBio, FEB 24, 2022, View Source [SID1234608951]).

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"Focused execution is our top priority in 2022 and we have a busy year ahead, with a strong set of catalysts across our pipeline. While we advance our high-quality programs, we are also taking steps to reduce our operating expenses and will continue to seek additional opportunities to extend our financial runway so that we can deliver meaningful medicines to patients in need as quickly as possible," said Neil Kumar, Ph.D., founder and CEO of BridgeBio.

BridgeBio’s key programs:

Acoramidis (AG10) – Transthyretin (TTR) stabilizer for transthyretin amyloid cardiomyopathy (ATTR-CM): The Company’s Phase 3 ATTRibute-CM study did not meet its primary endpoint of change from baseline in six-minute walk distance (6MWD) at Month 12. However, the Company did observe improvements in acoramidis-treated participants versus placebo-treated participants on the Kansas City Cardiomyopathy Questionnaire Overall Score (a quality-of-life measurement), N-terminal pro BNP (a biomarker of heart failure and independent predictor of survival in ATTR-CM), and serum TTR concentration (an in vivo reflection of TTR stabilization). Blinded all-cause mortality events in the ongoing study are consistent with the Company’s expectations given the severity of the enrolled population, the proportion of participants receiving drug and placebo, and the estimated therapeutic benefit of acoramidis. The Company remains confident in the Month 30 primary endpoint, a hierarchical composite including all-cause mortality and cardiovascular hospitalizations. Topline data from the trial are expected in mid-2023.

Encaleret – Calcium-sensing receptor (CaSR) inhibitor for autosomal dominant hypocalcemia type 1 (ADH1): BridgeBio presented preliminary Phase 2b data for encaleret in an oral presentation at the American Society of Bone and Mineral Research (ASBMR) 2021 Annual Meeting in October. Within five days of individualized dose titration in 13 participants, encaleret normalized mean blood calcium levels and 24-hour urine calcium excretion. Achieving simultaneous blood and urine calcium normalization is a challenge for patients with ADH1 due to the limitations of the current standard of care. If approved, encaleret could be the first therapy on the market for ADH1, a condition caused by gain of function variants in the CASR gene estimated to be carried by 12,000 individuals in the United States alone. BridgeBio plans to share complete data from the Phase 2b study in 2022. The Company also intends to initiate a Phase 3 registrational trial of encaleret in patients with ADH1 in 2022 and anticipates Phase 3 topline data in 2023.

Low-dose infigratinib – FGFR1-3 inhibitor for achondroplasia and hypochondroplasia: Initial proof-of-concept data from the ongoing Phase 2 dose-escalation and expansion study is anticipated in mid-2022. Achondroplasia is the most common form of genetic short stature and one of the most common genetic diseases, with a prevalence of over 55,000 cases in the United States and European Union. Low-dose infigratinib is the only known product candidate in clinical development for achondroplasia that is designed to target the disease at its genetic source and the only orally administered product candidate in clinical development.

BBP-631 – AAV5 gene therapy candidate for congenital adrenal hyperplasia (CAH): Dosed first patient in Phase 1/2 gene therapy trial in January 2022. Initial Phase 1/2 data readout anticipated in second half of 2022. Received Fast Track designation from the U.S. Food and Drug Administration (FDA) in May 2021. CAH is one of the most prevalent genetic diseases potentially addressable with adeno-associated virus (AAV) gene therapy, with more than 75,000 cases estimated in the United States and European Union. The disease is caused by deleterious mutations in the gene encoding an enzyme called 21-hydroxylase, leading to a lack of endogenous cortisol production. BBP-631 is designed to provide a functional copy of the 21-hydroxylase-encoding gene (CYP21A2) and potentially address many aspects of the disease course.

RAS cancer portfolio: BridgeBio announced the discovery of its next-generation KRAS G12C dual inhibitors, the first-known compounds that directly bind and inhibit KRAS in both its active (GTP bound) and inactive (GDP bound) conformations, and PI3ka:RAS breakers, small molecules that block RAS driven PI3Ka activation – a novel approach with the potential to inhibit oncogenic PI3Ka signaling without adverse effects on glucose metabolism. RAS is one of the most well-known oncogenic drivers with approximately 30% of all cancers being driven by RAS mutations, including large proportions of lung, colorectal and pancreatic tumors. BridgeBio expects to select a RAS development candidate in 2022.
Recent pipeline progress and corporate updates:

Debt financing: Secured up to $750 million in non-dilutive debt financing in November 2021. Innovative financing facility and existing cash balance gives BridgeBio access to over $1.2 billion, which is expected to fully fund the Company’s genetic disease and cancer pipeline programs into 2024.

Amgen clinical collaboration: Launched clinical collaboration with Amgen to study BBP-398, a potentially best-in-class SHP2 inhibitor, in combination with LUMAKRAS (sotorasib) in advanced solid tumors with the KRAS G12C mutation. The Phase 1/2 study will include a dose escalation period followed by dose expansion and optimization, and is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of BBP-398 in combination with LUMAKRAS. Under the terms of the non-exclusive collaboration, BridgeBio will sponsor the study and Amgen will provide a global supply of LUMAKRAS.

Helsinn Group strategic collaboration: Established strategic collaboration with the Helsinn Group to co-develop and co-commercialize BridgeBio’s novel GPX4 inhibitor in multiple cancer tumor types. BridgeBio and Helsinn established a non-exclusive framework agreement to identify and potentially co-develop and co-commercialize additional small molecule targeted oncology therapies. The collaboration builds on the $2.45 billion global license and collaboration agreement signed in March 2021 for development of BridgeBio’s FGFR inhibitor infigratinib in oncology indications.

TRUSELTIQ (infigratinib): BridgeBio partner Helsinn Group filed a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) in late 2021 for infigratinib as a second-line or later therapy in patients with advanced and/or metastatic cholangiocarcinoma (CCA) with fibroblast growth factor receptor 2 (FGFR2) fusions or translocations and received EMA acceptance of the MAA in December 2021, confirming that the submission is sufficiently complete to begin the formal review process. In September 2021 Health Canada approved TRUSELTIQ (infigratinib), a small molecule kinase inhibitor that targets FGFR, under the Notice of Compliance with Conditions (NOC/c) policy, for the treatment of adults with previously treated, unresectable locally advanced or metastatic CCA with a FGFR2 fusion or other rearrangement. Australia’s Therapeutic Goods Administration provisionally approved TRUSELTIQ (infigratinib) in November 2021.

BBP-418 – Glycosylation substrate for limb-girdle muscular dystrophy type 2i (LGMD2i): A Phase 2 trial was initiated in patients with LGMD2i in the first quarter of 2021. If successful, BBP-418 could be the first approved therapy for patients with LGMD2i. With approximately 7,000 patients with potentially treatable mutations, LGMD2i is an inherited recessive muscular dystrophy caused by mutation of fukutin-related protein. A top-line Phase 2 data readout is expected in early 2022. If the readout is successful, BridgeBio anticipates initiating a global Phase 3 clinical trial in the second half of 2022.

BBP-812 – AAV9 gene therapy candidate for Canavan disease: BridgeBio dosed the first patient in its Phase 1/2 trial of BBP-812 for Canavan disease in November 2021. If successful, BridgeBio’s gene therapy could be the first approved therapeutic option for children born with Canavan disease, a devastating and life-threatening condition. An initial Phase 1/2 data readout is expected in the second half of 2022.

BBP-671 – PanK activator for pantothenate kinase-associated neurodegeneration (PKAN) and organic acidemias: BridgeBio has completed the healthy volunteer portion of its Phase 1 trial, demonstrating initial tolerability, target engagement, and suitable PK for BBP-671. BBP-671 has received orphan drug designation as a treatment of propionic acidemia (PA) and PKAN in the United States and the European Union. BBP-671 has also been designated as a drug for a rare pediatric disease for treatment of both PKAN and PA. PKAN Phase 1 data is anticipated in the first half of 2022.

BBP-711 – Glycolate oxidase (GO) inhibitor for hyperoxaluria: Preliminary Phase 1 data showed that BBP-711 was well-tolerated and resulted in maximal increases in plasma glycolate exceeding those achieved by any GO-targeting agents reported in healthy adult volunteers. BBP-711 is being developed for the treatment of primary hyperoxaluria type 1 (PH1) and hyperoxaluria caused by hepatic overproduction of oxalate in recurrent kidney stone formers. A full readout of Phase 1 data in healthy adult volunteers is expected in 2022, to be followed by initiation of a Phase 2/3 trial in PH1 and a Phase 2 proof-of-concept trial in recurrent kidney stone formers.

BBP-589 – Recombinant collagen 7 for recessive dystrophic epidermolysis bullosa (RDEB): BridgeBio completed a Phase 2 clinical trial and anticipates providing data in early 2022. It has initiated a Phase 2 extension study, which will provide BBP-589 to two patients and extend dosing to six months.

BBP-398 – SHP2 inhibitor: BridgeBio is enrolling patients in a Phase 1 monotherapy dose escalation and expansion clinical trial in patients with RAS and RTK mutations. It anticipates providing a clinical update in mid-2022. A Phase 1 monotherapy expansion trial is anticipated to commence in the first half of 2022 to study patients with RTK and NF1 LOF mutations. In 2022, BridgeBio also plans to initiate Phase 1 combination trials with BBP-398 in combination with KRAS G12C, PD-1 and EGFR inhibitors. BridgeBio entered into a co-development agreement with Bristol Myers Squibb in July 2021 for the development of BBP-398 in combination with OPDIVO (nivolumab). BridgeBio launched a clinical collaboration with Amgen in January 2022 to study BBP-398 in combination with LUMAKRAS in advanced solid tumors with the KRAS G12C mutation. A Phase 1 clinical trial studying BBP-398 and osimertinib (EGFR) will be run in China by partner LianBio. LianBio has development and commercialization rights to BBP-398 in mainland China and other select Asian markets.
Fourth Quarter and Full Year 2021 Financial Results:

Cash, Cash Equivalents and Marketable Securities

Cash, cash equivalents and marketable securities, excluding restricted cash, totaled $787.5 million as of December 31, 2021, compared to $607.1 million as of December 31, 2020. Over the past year, the Company repurchased $150.0 million in BridgeBio common stock under its 2021 Share Repurchase Program and $50.0 million in BridgeBio common stock in conjunction with the issuance of its 2029 convertible notes, prepaid in full $124.1 million of term loans, paid $61.3 million for capped call options related to the issuance of its 2029 convertible notes, paid $35.0 million of regulatory-related milestone payments in connection with its FDA-approved products and paid $29.8 million in debt-related interests. Earlier during the year, BridgeBio paid $21.3 million to Eidos Therapeutics, Inc. (Eidos) shareholders who elected for cash settlement in exchange for their Eidos shares and $63.8 million in direct transaction costs arising from the merger with Eidos. These were offset by cash receipts of $731.4 million in net proceeds from the issuance of the 2029 convertible notes, $431.3 million in net proceeds from a loan and security agreement entered into with various lenders, $25.0 million in net proceeds from Hercules Capital, Inc. under an amended loan agreement, and collections of $72.6 million from collaboration partner Helsinn Group. The remaining change in cash, cash equivalents and marketable securities is primarily related to payments of operating costs and expenses.

Cash, cash equivalents and marketable securities, excluding restricted cash, increased by $187.9 million when compared to the balance as of September 30, 2021, which was $599.6 million. During the quarter, the Company received net proceeds of $431.3 million from the loan and security agreement entered into with various lenders and used a portion of the net proceeds to prepay in full the borrowings under the amended loan agreement with Hercules Capital, Inc. for $106.0 million.

Operating Costs and Expenses

Operating costs and expenses for the fourth quarter increased by $50.9 million to $178.5 million in the current quarter as compared to $127.6 million for the same period in the prior year. The increase in operating costs and expenses was due to an increase in personnel and external costs to support the progression of BridgeBio’s research and development programs and staged buildout of its commercial organization as part of commercial launch readiness activities. This increase in personnel and external costs was offset by $12.3 million in reimbursement of expenses from the cost sharing arrangement recognized under BridgeBio’s license and collaboration agreement with Helsinn Group. Stock-based compensation for the quarter was $22.5 million as compared to $12.1 million for the same period in the prior year.

The Company’s research and development expenses have not been significantly impacted by the global COVID-19 pandemic for the period presented. While BridgeBio experienced some delays in certain of its clinical enrollment and trial commencement activities, it continues to adapt in this unprecedented time to enable alternative site, telehealth and home visits, at-home drug delivery, as well as mitigation strategies with its contract manufacturing organizations. The longer-term impact, if any, of COVID-19 on BridgeBio’s operating costs and expenses is currently unknown.