On November 4, 2021 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported financial results for the third quarter 2021, and provided a corporate update on recent highlights and anticipated near-term milestones (Press release, Surface Oncology, NOV 4, 2021, View Source [SID1234594483]).

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"Surface continues to make considerable progress across our pipeline of novel cancer immunotherapies, highlighted by the announcement of our planned randomized Phase 2 study evaluating SRF388, our potential first-in-class antibody therapy against IL-27, in combination with Roche’s atezolizumab and bevacizumab," said Rob Ross, M.D., chief executive officer of Surface Oncology. "We believe more than ever in our approach targeting the adenosine pathway for the treatment of cancer and the potential of our next-generation antibody therapies in promoting immune activation in the tumor microenvironment. Looking ahead, we remain on track to provide clinical updates on our wholly-owned clinical programs, both as a single-agent and combination therapy, with data from SRF617 expected later this year, and SRF388 data expected in early 2022."

Third Quarter and Subsequent Corporate Highlights:

On November 2, 2021, Surface announced that two abstracts were accepted for presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting, taking place November 10-14, 2021, in Washington D.C. and virtually. The two abstracts will highlight new preclinical data from the Company’s two wholly-owned clinical-stage programs, SRF617 and SRF388.

On October 4, 2021, Surface announced details about its plan to initiate a randomized Phase 2 clinical study evaluating SRF388 in combination with Roche’s atezolizumab and bevacizumab, in patients with treatment-naïve hepatocellular carcinoma (HCC). Initiation-enabling activities are underway and the Company expects to dose the first patient in early 2022.

On July 8, 2021, Surface announced the appointment of Denice Torres to its board of directors as lead independent director. Ms. Torres has over 25 years of executive leadership experience in healthcare across the consumer, biopharmaceutical and medical device sectors.
Selected Anticipated Near-term Corporate Milestones:

Investigational New Drug (IND) filing for GSK4381562, formerly SRF813, targeting the PVRIG checkpoint and partnered with GlaxoSmithKline, will be filed in Q4 2021.

Data update for SRF617 anticipated at the European Society for Medical Oncology Immuno-Oncology Congress taking place December 8-11, 2021.

Data update for SRF388 anticipated in early 2022.
Financial Results:

As of September 30, 2021, cash, cash equivalents and marketable securities were $149.7 million, compared to $175.1 million on December 31, 2020.

Research and development (R&D) expenses were $14.0 million for the third quarter ended September 30, 2021, compared to $9.5 million for the same period in 2020. This increase was primarily driven by progress on both our SRF617 and SRF388 Phase 1 clinical trials. R&D expenses included $0.8 million in stock-based compensation expense for the third quarter ended September 30, 2021.

General and administrative (G&A) expenses were $5.8 million for the third quarter ended September 30, 2021, compared to $4.9 million for the same period in 2020. This increase was primarily due to increases in personnel and facility related costs. G&A expenses included $1.2 million in stock-based compensation expense for the third quarter ended September 30, 2021.

For the third quarter ended September 30, 2021, net loss was $19.9 million, or basic and diluted net loss per share attributable to common stockholders of $0.44. Net loss was $15.8 million for the same period in 2020, or basic and diluted net loss per share attributable to common stockholders of $0.39.

Financial Outlook:

In October 2021, Surface expanded its existing debt facility with K2 HealthVentures, increasing the capacity to $50M. Based upon its current operating plan and an anticipated near-term milestone from GSK, Surface maintains a projected cash runway through 2023.

On November 4, 2021 BeiGene (NASDAQ: BGNE; HKEX: 06160), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, reported clinical results and real world data from its hematology program to be presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, including two oral presentations on the Phase 3 SEQUOIA trial comparing BRUKINSA (zanubrutinib) to bendamustine and rituximab (B+R) in patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (Press release, BeiGene, NOV 4, 2021, View Source [SID1234594500]). The ASH (Free ASH Whitepaper) meeting will take place on December 11-14, 2021, as a hybrid event in Atlanta, GA and in a virtual format.

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Jane Huang, M.D., Chief Medical Officer of Hematology at BeiGene, commented: "Together with ALPINE, the positive SEQUOIA trial provides evidence that BRUKINSA can improve treatment outcomes for patients with CLL. Data at ASH (Free ASH Whitepaper) this year reinforce our belief that BRUKINSA’s differentiated design can bring patients clinical benefits, including those who experience treatment discontinuation with other BTK inhibitors. We look forward to sharing more details on our clinical progress in our hematology portfolio with the medical community in Atlanta."

BRUKINSA Shows Promise in Improving CLL Treatment Outcomes with Positive Results in SEQUOIA (vs. B+R) and ALPINE (vs. Ibrutinib)

Following the positive ALPINE trial of BRUKINSA versus ibrutinib in patients in the relapsed or refractory (R/R) setting in June 2021, BRUKINSA demonstrated superiority over B+R as a first-line treatment for patients with CLL in SEQUOIA, the second positive Phase 3 trial of BRUKINSA in CLL.

Data from the randomized Cohort 1 of SEQUOIA met the primary endpoint at interim analysis, with BRUKINSA achieving a highly statistically significant improvement in progression-free survival (PFS) compared to B+R regimen. Efficacy results were consistent between independent review committee (IRC) and investigator assessments, with a hazard ratio (HR) of 0.42 for both, and were observed across patient characteristics. The data also demonstrated superiority in efficacy measured by overall response rate (ORR) as assessed by both IRC and investigator. Similar to data observed in its broad global clinical program, BRUKINSA was generally well-tolerated in patients with CLL. In particular, low rates of a key safety measurement—atrial fibrillation—were observed in the SEQUOIA trial, consistent with data from ASPEN and ALPINE, the two head-to-head Phase 3 trials of BRUKINSA versus ibrutinib.

In addition, early safety results from the ongoing Cohort 3 (Arm D) evaluating BRUKINSA in combination with Bcl-2 inhibitor venetoclax for CLL patients with del(17p), a high-risk characteristic, suggested a good tolerability profile of the combination.

Additional Data at ASH (Free ASH Whitepaper) Support BRUKINSA’s Potential as an Alternative for Patients Intolerant to Other BTK Inhibitors

To address tolerability issues commonly seen in other BTK inhibitors, BRUKINSA was purposefully designed to optimize selectivity to avoid off-target effects. In the ongoing Phase 2 trial BGB-3111-215 in patients with relapsed or refractory (R/R) B-cell malignancies who were intolerant to prior treatment with other approved BTK inhibitors, continued disease control or improved responses were observed with BRUKINSA treatment. The majority of patients (73%) on BRUKINSA did not experience recurrence of adverse events that led to treatment discontinuation with other BTK inhibitors.

BeiGene Presentations at the 63rd ASH (Free ASH Whitepaper) Annual Meeting

Abstract Information

Date and Time

Presenting Author

Oral Presentations

#396: SEQUOIA: Results of a Phase 3 Randomized Study of Zanubrutinib versus Bendamustine + Rituximab (BR) in Patients with Treatment-Naïve (TN) Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (CLL/SLL)

642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological I

Sun, Dec 12

10:45 AM ET

Constantine Tam

#67: Zanubrutinib in Combination with Venetoclax for Patients with Treatment-Naïve (TN) Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) with del(17p): Early Results from Arm D of the SEQUOIA (BGB-3111-304) Trial

642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological I

Sat, Dec 11

10:45 AM ET

Alessandra Tedeschi

Poster or Mini Oral Presentations

#1410: Phase 2 Study of Zanubrutinib in BTK Inhibitor-Intolerant Patients (Pts) With Relapsed/Refractory B-cell Malignancies

626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster I

Sat, Dec 11

5:30 PM ET

Mazyar Shadman

#1419: Preliminary Safety and Efficacy Data from Patients (Pts) With Relapsed/Refractory (R/R) B-cell Malignancies Treated with the Novel B-cell Lymphoma 2 (BCL2) Inhibitor BGB-11417 in Monotherapy or in Combination with Zanubrutinib

626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster I

Sat, Dec 11

5:30 PM ET

Constantine Tam

#3540: Preliminary Safety and Efficacy from a Multicenter, Investigator-Initiated Phase II Study in Untreated TP53 Mutant Mantle Cell Lymphoma with Zanubrutinib, Obinutuzumab, and Venetoclax (BOVen)

623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster III

Mon, Dec 13

6:00 PM ET

Anita Kumar

#4078: Real-World Testing Patterns for Risk Assessment and Implications on the Adoption of Novel Therapeutics in Chronic Lymphocytic Leukemia: IGHV Mutation Status, FISH Cytogenetic, and Immunophenotyping

905. Outcomes Research—Lymphoid Malignancies: Poster III

Mon, Dec 13

6:00 PM ET

Asher Chanan-Khan

#3046: Real-World Bruton Tyrosine Kinase Inhibitor Treatment Patterns, Compliance, Costs, and Hospitalizations in Patients with Mantle Cell Lymphoma in the United States

905. Outcomes Research—Lymphoid Malignancies: Poster II

Sun, Dec 12

6 PM ET

Bijal Shah

#4009: Productivity Loss and Indirect Costs Among Non-Hodgkin Lymphoma Patients and Their Caregivers

902. Health Services Research—Lymphoid Malignancies: Poster III

Mon, Dec 13

6:00 PM ET

Asher Chanan-Khan

#4077: Impact of Atrial Fibrillation on Cardiovascular and Economic Outcomes in Patients with Chronic Lymphocytic Leukemia

905. Outcomes Research—Lymphoid Malignancies: Poster III

Mon, Dec 13

6:00 PM ET

Anjana Mohan

#4079: Real-World Treatment Patterns, Adherence and Healthcare Resource Utilization for Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia Among Veterans in the United States

905. Outcomes Research—Lymphoid Malignancies: Poster III

Mon, Dec 13

6:00 PM ET

Asher Chanan-Khan

#3048: Real-World Disease Burden, Costs and Resource Utilization of Hospital-Based Care Among Mantle Cell Lymphoma, Waldenström Macroglobulinemia, Marginal Zone Lymphoma and Chronic Lymphocytic Leukemia: Disparities and Risk Factors

905. Outcomes Research—Lymphoid Malignancies: Poster II

Sun, Dec 12

6 PM ET

Asher Chanan-Khan

#1968: Factors Associated with Treatment Among Older Adults Diagnosed with Chronic Lymphocytic Leukemia: An Analysis Using Medicare Claims Data

905. Outcomes Research—Lymphoid Malignancies: Poster I

Sat, Dec 11

5:30 PM ET

Eberechukwu Onukwugha

About BRUKINSA

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.

BRUKINSA is approved in the following indications and regions:

For the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (United States, November 2019)*;
For the treatment of MCL in adult patients who have received at least one prior therapy (China, June 2020)**;
For the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in adult patients who have received at least one prior therapy (China, June 2020)**;
For the treatment of relapsed or refractory MCL (United Arab Emirates, February 2021);
For the treatment of Waldenström’s macroglobulinemia (WM) in adult patients (Canada, March 2021);
For the treatment of adult patients with WM who have received at least one prior therapy (China, June 2021)**;
For the treatment of MCL in adult patients who have received at least one prior therapy (Canada, July 2021);
For the treatment of MCL in adult patients who have received at least one prior therapy (Chile, July 2021);
For the treatment of adult patients with MCL who have received at least one previous therapy (Brazil, August 2021);
For the treatment of adult patients with WM (United States, August 2021);
For the treatment of adult patients with marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen (United States, September 2021)*;
For the treatment of adult patients with MCL who have received at least one previous therapy (Singapore, October 2021);
For the treatment of MCL in patients who have received at least one prior therapy (Israel, October 2021);
For the treatment of adult patients with WM who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy (Australia, October 2021);
For the treatment of adult patients with MCL who have received at least one prior therapy (Australia, October 2021); and
For the treatment of adult patients with MCL who have received at least one previous therapy (Russia, October 2021).
*

This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

This indication was approved under conditional approval. Complete approval for this indication may be contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

To-date, more than 30 marketing authorization applications in multiple indications have been submitted in the United States, China, the European Union, and more than 20 other countries or regions.

BeiGene Oncology

BeiGene is committed to advancing best and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D team of approximately 2,300 colleagues dedicated to advancing more than 90 clinical trials involving more than 13,000 patients and healthy volunteers. Our expansive portfolio is directed by a predominantly internalized clinical development team supporting trials in more than 40 countries. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. We currently market three medicines discovered and developed in our labs: BTK inhibitor BRUKINSA in the United States, China, Canada, Australia and additional international markets; and non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab and PARP inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen and Bristol Myers Squibb. We also plan to address greater areas of unmet need globally through our collaborations including with Amgen, Bio-Thera, EUSA Pharma, Mirati Therapeutics, Seagen, and Zymeworks. BeiGene has also entered into a collaboration with Novartis granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.

On November 4, 2021 Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to cures for cancer and other serious diseases, reported that Aviad Pato, Ph.D., Head of Immunology Research, presented data on two nicotinamide (NAM)-enabled NK cell therapies, GDA-501 and GDA-301, at the Protein & Antibody Engineering Summit (PEGS) Europe taking place in Barcelona, Spain, and virtually November 2-4, 2021 (Press release, Gamida Cell, NOV 4, 2021, View Source [SID1234594517]).

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The presentation included data from early-stage studies of GDA-501, Gamida Cell’s investigational cell therapy comprised of CAR-engineered NK cells designed to enhance homing and activation against cancers with HER2 overexpression such as breast, ovarian, lung, bladder, and gastric cancers. Data were also presented on GDA-301, which combines a CRISPR/Cas9 knockout of the CISH (cytokine inducible SH2 containing protein) gene in NK cells with a membrane-bound IL-15/IL-15Ra CAR, which is designed to improve tumor killing by promoting activation and inhibiting negative feedback signals and has potential application in a range of solid tumors and hematologic malignancies.

Data presented by Gamida Cell demonstrated that the engineered GDA-501 NK enhances potency and cytotoxicity against a HER2-expressing tumor cell line. Data also showed that GDA-301 has cytotoxic activity against a chronic myelogenous leukemia cell line (K562) and a multiple myeloma cell line (RPMI).

"The field of NK cell immunotherapy is advancing beyond what has previously been understood from T cell gene editing," said Yona Geffen, Ph.D., Vice President, Research and Development at Gamida Cell. "We are pleased to share this important update on two key potential therapies in Gamida Cell’s robust NK pipeline that show their potential as clinical immunotherapy agents."

The full presentation shared at PEGS Europe is available at www.gamida-cell.com.

On November 4, 2021 ADC Therapeutics SA (NYSE: ADCT), a commercial-stage biotechnology company improving the lives of those affected by cancer with its next-generation, targeted antibody drug conjugates (ADCs) for patients with hematologic malignancies and solid tumors, reported abstracts for ZYNLONTA and ADCT-602 have been accepted for presentations at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, which will be held virtually and in Atlanta, Georgia from December 11-14, 2021 (Press release, ADC Therapeutics, NOV 4, 2021, View Source [SID1234594535]).

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"We look forward to sharing data on our targeted ADCs as single agents and in innovative combinations at the 2021 ASH (Free ASH Whitepaper) Annual Meeting," said Joseph Camardo, MD, Chief Medical Officer of ADC Therapeutics. "This will include presentations from investigators on subset data from our pivotal Phase 2 study and data on the use of ZYNLONTA post-CAR-T. We are also encouraged by the anti-tumor activity and manageable safety profile of ZYNLONTA in combination with ibrutinib. The Phase 2 protocol has recently been amended with a higher and more frequent dose of ZYNLONTA to potentially enhance the response and to investigate this combination in earlier lines of therapy."

Details of ADC Therapeutics’ oral presentation are as follows:

Planned Interim Analysis of a Phase 2 Study of Loncastuximab Tesirine Plus Ibrutinib in Patients with Advanced Diffuse Large B-Cell Lymphoma (LOTIS-3)
Abstract: 54
Date and Time: Saturday, December 11, 2021, 10:45 a.m. EST
Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Population data for Aggressive NHL Management
Presenter: Carmelo Carlo-Stella, MD, Department of Biomedical Sciences, Humanitas University, and Department of Oncology and Hematology, IRCCS Humanitas Research Hospital, Milan, Italy

Details of ADC Therapeutics’ poster presentations are as follows*:

Clinical Characteristics and Responses of Patients with Relapsed or Refractory High-Grade B-cell Lymphoma Treated with Loncastuximab Tesirine in the LOTIS-2 Clinical Trial
Abstract: 3575
Date: Monday, December 13, 2021
Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster III
Presenter: Juan Pablo Alderuccio, MD, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA

Combination of Loncastuximab Tesirine and Polatuzumab Vedotin Shows Increased Anti-Tumor Activity in Pre-Clinical Models of Non-Hodgkin Lymphoma
Abstract: 2273
Date: Sunday, December 12, 2021
Session: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II
Presenter: Francesca Zammarchi, PhD, ADC Therapeutics

CD19-mediated DNA Damage Boost in Lymphoma Cells Treated with Loncastuximab Tesirine in Combination with PARP inhibitors
Abstract: 1342
Date: Saturday, December 11, 2021
Session: 622. Lymphomas: Translational—Non-Genetic: Poster I
Presenter: Stefania Fusani, PhD, Oncohematology Division, IEO Istituto Europeo di Oncologia IRCCS, Milano, Italy

Details of an independently developed ZYNLONTA poster are as follows:

The Anti-CD19 Antibody-Drug Conjugate Loncastuximab Tesirine Achieved Responses in Patients with Diffuse Large B-cell Lymphoma Who Relapsed After Anti-CD19 CAR T-Cell Therapy
Abstract: 2489
Date: Sunday, December 12, 2021
Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster II
Presenter: Paolo F. Caimi, MD, Cleveland Clinic/Case Comprehensive Cancer Center, Cleveland, OH, USA

Details of an independently developed ADCT-602 poster are as follows:

A Phase 1 Trial of ADCT-602, a CD22 Targeting Antibody Drug Conjugate Bound to PBD Toxin in Adult Patients with Relapsed or Refractory CD22+ B-Cell Acute Lymphoblastic Leukemia
Abstract: 1237
Date: Saturday, December 11, 2021
Session: 614. Acute Lymphoblastic Leukemias: Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster I
Presenter: Nitin Jain, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

*Posters will be available in the poster exhibit hall in the Georgia World Congress Center on these dates: December 11: 9:00 a.m.–7:30 p.m. EST; December 12 & 13: 9:00 a.m.–8:00 p.m. EST. Presenters planning to attend in-person are expected to present during the final two hours of the noted viewing time.

The abstracts are available through the ASH (Free ASH Whitepaper) online meeting program and will be published in the November supplemental issue of Blood.

About ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death.

The U.S. Food and Drug Administration (FDA) has approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ZYNLONTA is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.

On November 4, 2021 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 third quarter ended September 30, 2021 and provided an update on the Company’s operations (Press release, BridgeBio, NOV 4, 2021, View Source [SID1234594564]).

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BridgeBio has more than 30 programs in its pipeline for patients living with genetic diseases and cancers and 20 ongoing clinical trials underway across more than 450 sites around the world. Earlier this year BridgeBio received its first two U.S. Food and Drug Administration (FDA) drug approvals and has successfully filed 15 Investigational New Drug (IND) applications since the Company’s founding in 2015.

BridgeBio’s four core value drivers:

Acoramidis (AG10) – Transthyretin (TTR) stabilizer for transthyretin amyloid cardiomyopathy (ATTR-CM): Topline results from Part A of the Phase 3 ATTRibute-CM trial are expected in late 2021 and from Part B in 2023. The primary endpoint at Part A is the change from baseline in a 6-minute walk distance (6MWD) in trial participants receiving acoramidis or placebo after 12 months. If the change from baseline in 6MWD in Part A is highly statistically significant, BridgeBio expects to submit an application for regulatory approval of acoramidis in 2022 to the FDA. The study enrolled more than 600 subjects with either wild-type or variant TTR across more than 80 sites in 18 countries. ATTR-CM is a rare heart condition with a progressive and debilitating impact on quality of life likely affecting more than 400,000 patients worldwide.
Encaleret – Calcium-sensing receptor (CaSR) inhibitor for autosomal dominant hypocalcemia type 1 (ADH1): BridgeBio presented updated 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 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 calcium-sensing receptor (CASR) gene estimated to be carried by 12,000 individuals in the United States alone. BridgeBio plans to initiate a Phase 3 registrational trial of encaleret in patients with ADH1 in 2022.
Low-dose infigratinib – FGFR1-3 inhibitor for achondroplasia: Initial data from the ongoing Phase 2 dose ranging study are expected in the first half of 2022. Achondroplasia is the most common form of genetic short stature and one of the most common genetic diseases, with a prevalence of greater than 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-stage development.
BBP-631 – AAV5 gene therapy candidate for congenital adrenal hyperplasia (CAH): Received Fast Track designation from the FDA in May 2021. IND cleared by the FDA and site activation for initiation of a first-in-human Phase 1/2 study is ongoing, with initial data anticipated in mid-2022. CAH is one of the most prevalent genetic diseases potentially addressable with 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 lack of endogenous cortisol production. BridgeBio’s AAV5 gene therapy candidate is designed to provide a functional copy of the 21-hydroxylase-encoding gene (CYP21A2) and potentially address many aspects of the disease course.
Recent pipeline progress and corporate updates:

Stock repurchases: BridgeBio repurchased $148.4 million in BridgeBio common stock under its 2021 Share Repurchase Program, demonstrating the Company’s confidence in the long-term prospects of its pipeline.
LianBio IPO and partnership: China-based partner LianBio raised $325 million in its initial public offering on November 1. BridgeBio is estimated to own approximately 4.7% post-IPO. BridgeBio and LianBio announced in August that the first patient was treated in a Phase 2a trial of infigratinib in patients with gastric cancer and other advanced solid tumors. LianBio in-licensed rights from BridgeBio for infigratinib for development and commercialization in Mainland China, Hong Kong and Macau.
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.
BBP-812 – AAV9 gene therapy candidate for Canavan disease: BridgeBio announced that the first patient was dosed in its Phase 1/2 trial of BBP-812 for Canavan disease. 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 2022.
BBP-818 – AAV gene therapy candidate for classic galactosemia (severe GALT deficiency): BridgeBio announced a new gene therapy program for classic galactosemia, which is caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT), affecting approximately 7,000 patients in the United States and the European Union. Preclinical studies in a mouse model of classic galactosemia have shown that BridgeBio’s BBP-818 therapy restored up to 72% of wild-type levels of GALT enzyme in the brain following a single dose.
BBP-398 – SHP2 inhibitor: First publication of preclinical data for BridgeBio’s potentially best-in-class SHP2 inhibitor designed for the treatment of resistant cancer. Data demonstrated activity in non-small cell lung cancer (NSCLC) driven by RAS or other MAPK-pathway activating mutations. The results were featured in a poster presentation shared at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in October.
BBP-418 – Glycosylation substrate for limb-girdle muscular dystrophy type 2i (LGMD2i): Fast Track designation granted by the FDA. The 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 Phase 2 data readout is expected in 2022.
BBP-711 – Glycolate oxidase (GO) inhibitor for hyperoxaluria: BridgeBio announced preliminary Phase 1 data in which 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.
TRUSELTIQ (infigratinib): Health Canada approved TRUSELTIQ (infigratinib), a small molecule kinase inhibitor that targets fibroblast growth factor receptor (FGFR), under the Notice of Compliance with Conditions (NOC/c) policy, for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma (CCA) with a FGFR2 fusion or other rearrangement. BridgeBio’s partner Helsinn Group has exclusive commercial rights for TRUSELTIQ in Canada with BridgeBio eligible for tiered royalties as a percentage of net sales as part of the global collaboration and license agreement entered into between the two companies in March 2021.
BridgeBio Pharma R&D Day: Held a virtual R&D Day on October 12, 2021. Presentation replay can be found on BridgeBio’s investor website here.
Four new independent directors added to BridgeBio’s board:
Hannah Valantine, M.D., a leader in organ transplant genomics and workforce diversity who is a professor of medicine at Stanford University School of Medicine
Fred Hassan, a pharmaceutical and financial industry leader who is the former CEO of Schering-Plough and former chairman of Bausch & Lomb
Andrea Ellis, a consumer technology innovator and the chief financial officer of Lime
Douglas Dachille, an investment management veteran and the former chief investment officer of American International Group, Inc. (AIG)
Third Quarter 2021 Financial Results:

Cash, Cash Equivalents and Marketable Securities

Cash, cash equivalents and marketable securities, excluding restricted cash, totaled $599.6 million as of September 30, 2021, compared to $607.1 million as of December 31, 2020. Over the past three quarters, the Company repurchased $148.4 million in BridgeBio common stock under its 2021 Share Repurchase Program and $50.0 million in BridgeBio common stock in conjunction with its issuance of the 2029 convertible notes, paid $61.3 million for capped call options related to the issuance of its 2029 convertible notes and $35.0 million of regulatory-related milestone payments in connection with its approved products. Earlier during the year, BridgeBio paid $21.3 million to Eidos shareholders who elected for cash settlement in exchange for their Eidos shares and $63.8 million of 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 BridgeBio’s 2029 convertible notes, $65.1 million from collaboration partner, Helsinn Group, and $25.0 million in net proceeds from Hercules Capital, Inc. under an amended loan agreement. The remaining change primarily related to payments of interest and operating costs and expenses.

Cash, cash equivalents and marketable securities, excluding restricted cash decreased by $298.8 million when compared to balance as of June 30, 2021, which was $898.4 million. During the quarter, the Company repurchased $143.1 million of BridgeBio common stock and paid $35.0 million of regulatory-related milestone payments in connection with its approved products.

Operating Costs and Expenses

Operating costs and expenses for the quarter increased by $23.7 million to $151.8 million in the current quarter as compared to $128.1 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 in 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 $12.2 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 $16.1 million as compared to $17.7 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 periods 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.