On October 7, 2021 BridgeBio Pharma, Inc. (Nasdaq: BBIO), a commercial-stage biopharmaceutical company that focuses on genetic diseases and cancers, reported preclinical findings for its SHP2 inhibitor, BBP-398, in non-small cell lung cancer (NSCLC) (Press release, BridgeBio, OCT 7, 2021, View Source [SID1234590923]). The results are featured in a poster presentation titled ‘BBP-398, a potent, small molecule inhibitor of SHP2, enhances the response of established NSCLC xenografts to KRASG12C and EGFRmut inhibitors’ 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) taking place virtually on October 7 – 10, 2021.

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"We are excited to share our promising preclinical data in non-small cell lung cancer models, which provides a critical step in understanding the potential that BBP-398 has for patients with tumors driven by RAS or other MAPK-pathway activating mutations," said Eli Wallace, Ph.D., chief scientific officer at BridgeBio Oncology. "For patients with this type of progressive cancer, there is a serious need for more innovative medicines to be accessible as quickly as possible. Our potentially best-in-class SHP2 inhibitor could be an ideal combination agent for certain cancer patients given its promising profile of preclinical results and potential for once daily dosing."

BBP-398, developed in collaboration with the University of Texas MD Anderson Cancer Center’s Therapeutics Discovery division, exhibits preclinical monotherapy efficacy in RTK/KRAS-driven xenograft models as well as synergy in combination with both sotorasib and osimertinib. The predicted human steady-state plasma concentration-time profiles suggest continuous once daily oral dosing of BBP-398 may achieve the desired therapeutic index for patients.

BridgeBio is currently advancing its Phase 1 dose escalation clinical trial with its SHP2 inhibitor, BBP-398, in patients with solid tumors driven by mutations in the MAPK signaling pathway, including RAS and receptor tyrosine kinase genes. More than 30% of all human cancers – including 95% of pancreatic cancers and 45% of colorectal cancers — are driven by mutations of the RAS family of genes.

BridgeBio’s precision oncology programs are driven by the Company’s molecular dynamics and RAS structural biology platforms, which are enabled by our broad partnerships with the Lawrence Livermore National Laboratory and National RAS Initiative, respectively.

BridgeBio’s SHP2 inhibitor, BBP-398, is one of the Company’s 14 programs that are in the clinic or commercial setting for patients living with genetic diseases and genetically-driven cancers.

Learn more about the preclinical data for BBP-398 at BridgeBio’s upcoming virtual R&D Day on Tuesday, October 12, 2021 at 8:30 am ET. The event will be webcast and registration information can be found here.

BridgeBio will unveil new programs, share new information about its pipeline and discuss how it is broadening the scope of its R&D engine. It will also cover the Company’s most significant near-term catalysts with a focus on the upcoming topline results for acoramidis, BridgeBio’s investigational therapy for transthyretin (TTR) amyloidosis (ATTR). ATTR is a rare heart condition with a progressive and debilitating impact on quality of life likely affecting more than 400,000 patients worldwide.

Topline acoramidis results from Part A 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 U.S. Food and Drug Administration.

The R&D Day program importantly and additionally will highlight BridgeBio’s broader efforts in cardiorenal, progress in its KRAS portfolio, and advancements in its previously disclosed early-stage Mendelian programs. The Company will also be unveiling new investigational programs in gene therapy.

About SHP2
SHP2 is a protein-tyrosine phosphatase that links growth factor, cytokine and integrin signaling with the downstream RAS/ERK MAPK pathway to regulate cellular proliferation and survival. Overactivity of the SHP2 pathway, often driven by distinct genetic mutations, is a critical contributor to many forms of cancer, and is a mechanism of resistance to several targeted therapies. Estimated to affect approximately 500,000 patients in the United States and the European Union, cancers that are driven by hyperactive MAPK signaling, including certain RAS mutations such as KRASG12C, may be sensitive to SHP2 inhibition.

About BBP-398
BBP-398 is a potent, selective, orally bioavailable SHP2 inhibitor that demonstrates pathway inhibition across a panel of cell lines with active MAPK signaling. The therapy is designed to be optimized for continuous once daily dosing through its pharmacokinetic profile. The inhibitor was developed through a collaboration with the University of Texas MD Anderson Cancer Center’s Therapeutics Discovery division. BridgeBio has a non-exclusive, co-funded clinical collaboration with Bristol Myers Squibb to evaluate the combination of BBP-398 with OPDIVO (nivolumab) in patients with advanced solid tumors with KRAS mutations. The collaboration will also include the initiation of a Phase 1/2 study to evaluate the safety and preliminary efficacy of BBP-398 in combination with both OPDIVO as doublet therapy, and OPDIVO plus a KRASG12C inhibitor as triplet therapy in non-small cell lung cancer (NSCLC) with KRAS mutations, as first- and second-line treatment options. Additionally, BridgeBio previously entered into a strategic collaboration with LianBio for clinical development and commercialization of BBP-398 in combination with various agents in solid tumors such as non-small cell lung cancer, colorectal and pancreatic cancer, in mainland China and other major Asian markets.

On October 7, 2021 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies to treat cancer, reported NKX019 and NKX101 clinical development program updates (Press release, Nkarta, OCT 7, 2021, View Source [SID1234590938]).

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Patients have been dosed in the international Phase 1 clinical trial of NKX019 in advanced B-cell malignancies. NKX019 is an NK cell immunotherapy that is engineered to eradicate tumors expressing CD19, a validated B-cell cancer target.

"We are excited to explore the potential of NKX019, our second clinical-stage, engineered chimeric antigen receptor (CAR) NK cell therapy candidate, to become a leading treatment of B-cell malignances for eventual use in a broadly accessible outpatient setting," said Paul J. Hastings, President and Chief Executive Officer of Nkarta. "NKX019 builds upon the potent innate anti-tumor biology and promising safety profile of natural killer cells. This trial moves us one step closer to bringing game-changing, off-the-shelf cell therapies to cancer patients. We anticipate reporting initial data from the NKX019 study in 2022."

Nkarta is producing the clinical supply of NKX019 at its in-house cGMP clinical manufacturing facility in South San Francisco, California.

Nkarta is also updating guidance on when it expects to announce initial data from the first-in-human Phase 1 clinical trial of NKX101, an engineered CAR NK cell therapy candidate targeting the NKG2D ligand, in patients with relapsed or refractory acute myeloid leukemia (AML) or higher-risk myelodysplastic syndromes (MDS) to the first half of 2022.

Multiple factors have affected the cadence of the NKX101 Phase 1 study, including the use of haplomatched donor derived cells in the original study design, requirement for a staggered enrollment of patients that was longer than originally expected, and COVID-19 related disruptions. As previously announced, the clinical trial protocol was later amended in consultation with the U.S. Food and Drug Administration to be able to dose patients with either off-the-shelf or haplomatched cells, shorten the stagger between certain patients, and introduce a second parallel dosing regimen. The new timing is intended to allow Nkarta to report a robust data set from the study, which is currently enrolling patients at several locations in the United States.

About the NKX019-101 Clinical Trial
The NKX019-101 clinical trial is a Phase 1, multi-center, open-label, dose-finding and dose-expansion study to evaluate the safety and anti-tumor activity of NKX019 as a multi-dose, multi-cycle monotherapy. Patients with CAR T naïve relapsed/refractory non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) or B-cell acute lymphoblastic leukemia (B-ALL) will be enrolled in the dose-finding portion of the study. Following the selection of a recommended Phase 2 dose, patients with r/r B-ALL, CLL, or other subtypes of NHL, including patients who did not achieve a durable response after treatment with a CD19 CAR T cell therapy, will be enrolled in the dose-expansion portion of the trial. To learn more about the clinical trial of NKX019 in advanced B cell malignancies, please visit ClinicalTrials.gov.

About NKX019
NKX019 is an investigational, allogeneic, off-the-shelf cancer immunotherapy that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed CAR for enhanced tumor cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal and malignant B cells, and it is a validated target for B cell cancer therapies.

About NKX101
NKX101 is an investigational, off-the-shelf cancer immunotherapy that uses natural killer (NK) cells derived from the peripheral blood of healthy donors and engineered with membrane-bound IL-15 and a chimeric antigen receptor (CAR) targeting NKG2D ligands on tumor cells. NKG2D, a key activating receptor found on naturally occurring NK cells, induces a cell-killing immune response through the detection of stress ligands that are widely expressed on cancer cells. By engineering NKX101 with the proprietary NKG2D-based CAR, the ability of NK cells to recognize and kill tumor cells in pre-clinical models is increased significantly compared to non-engineered NK cells. The addition of membrane-bound IL15, a proprietary version of a cytokine for activating NK cell growth, has been shown in pre-clinical models to enhance the proliferation, persistence and sustained activity of NK cells. To learn more about the NKX101 clinical trial in adults with AML or MDS, please visit ClinicalTrials.gov.

About B-Cell Cancers
B-cell lineage cancers are a worldwide healthcare burden. Over 500,000 new cases of non-Hodgkin lymphoma (NHL) and 50,000 new cases of acute lymphoblastic leukemia (ALL) are diagnosed world-wide each year (seer.cancer.gov, Smith 2015, Solomon 2017). Despite progress in treatment, many patients diagnosed with this heterogeneous group of cancers still succumb to their diseases. Autologous chimeric antigen receptor (CAR) T cells specific for CD19 have altered the treatment landscape for some patients with relapsed or refractory B-cell malignancies, though significant toxicities associated with T-cell expansion and the necessity for bespoke manufacturing have limited their use.

About AML and MDS
Acute Myeloid Leukemia (AML) is a rapidly progressing blood cancer caused by abnormalities of myeloid cells, a cell type in the bone marrow that would normally develop into different types of blood cells. AML usually worsens rapidly and can lead to death if not treated. Over 120,000 new cases of AML are diagnosed world-wide each year.* Despite recent advancements, an unmet need for novel treatment options remains high. After treatment with approved therapies for AML, many patients either do not achieve complete response (CR) or relapse after CR. There is no approved therapy and limited treatment options for patients with relapsed or refractory (r/r) AML. CR rates of 12% to 18% with repeated cycles of chemotherapy are reported in this patient population.**

Myelodysplastic Syndromes (MDS) are a group of bone marrow disorders in which the blood-forming cells in the bone marrow do not produce enough healthy blood cells. Some patients with MDS have too many young, immature blood-making cells in the bone marrow. The median overall survival rate of higher risk MDS patients is 0.8 to 3.0 years. There is currently no curative treatment for patients who relapse after front-line therapy or do not respond to front-line therapy. MDS can progress to AML in about one-third of patients.

*Ming Yi et al, J Hematol Oncol. 2020; 13: 72.
**Roboz et al, JCO 2014; 32: 18. Faderl et al, JCO 2012; 30: 20. Ravandi et al, Lancet 2015; 16: 9.

On October 7, 2021 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported a non-exclusive clinical collaboration agreement with Sanofi to evaluate the combination of adagrasib, the Company’s investigational KRASG12C inhibitor, with Sanofi’s investigational SHP2 inhibitor SAR442720, also known as RMC-4630 (Press release, Mirati, OCT 7, 2021, View Source [SID1234590960]). The Phase 1/2 dose escalation and expansion study will evaluate the combination in patients with previously-treated non-small cell lung cancer (NSCLC) and KRASG12C mutations.

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"Mirati is aggressively advancing a broad adagrasib development program, which includes pursuing novel combination approaches including through this collaboration with Sanofi," said Charles M. Baum, M.D., Ph.D., president, founder and head of research and development, Mirati Therapeutics, Inc. "There is strong scientific rationale for combining a SHP2 inhibitor with adagrasib, which may help optimize clinical outcomes for patients with KRASG12C-dependent tumors."

SHP2 is upstream of KRAS and mediates cellular signaling through the RAS/MAP kinase pathway and is frequently overactive in various types of cancer. KRASG12C inhibition and SHP2 inhibition have complementary mechanisms of action and have demonstrated additive anti-tumor activity in pre-clinical models.

Under the terms of the agreement, Sanofi will be responsible for sponsoring and operating the Phase 1/2 study, and jointly with Mirati, will oversee and share costs of the study.

About Adagrasib (MRTX849)

Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C mutated cancers, as the KRASG12C protein regenerates every 24−48 hours. Adagrasib is a being evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including non-small cell lung cancer (NSCLC), colorectal cancer and pancreatic cancer. For more information visit Mirati.com/science.

About SAR442720 (RMC-4630)

SAR442720 (RMC-4630) is a potent and orally bioavailable small molecule that is designed to selectively inhibit the activity of SHP2, an upstream cellular protein that plays a central role in modulating cell survival and growth by transmitting signals from receptor tyrosine kinases to RAS. SAR442720 (RMC-4630) is the focus of an exclusive global development and commercialization agreement between Sanofi and Revolution Medicines.

On October 7, 2021 NorthStar Medical Radioisotopes, LLC, a global innovator in the development, production and commercialization of radiopharmaceuticals used for therapeutic applications and medical imaging, reported the launch of its newly redesigned corporate website (Press release, NorthStar Medical Radiostopes, OCT 7, 2021, View Source [SID1234590982]). The new site includes increased functionality and a number of enhancements. Expanded content includes latest product information, updates on NorthStar’s significant campus expansion, its growing partnerships and dynamic pipeline in therapeutic and SPECT radiopharmaceuticals, and the latest in career opportunities as the Company continues to grow and expand. NorthStar welcomes visitors to its new site at: www.northstarnm.com.

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"We are very pleased to launch the new NorthStar corporate website that reflects our excitement and enthusiasm in working to provide global solutions for reliable medical radioisotope supply for patient health," said Stephen Merrick, President and Chief Executive Officer of NorthStar Medical Radioisotopes. "We redesigned the website to provide details on NorthStar’s progress and expansion, our talented and experienced management team and employee base, our robust plans for the future and our commitment to patient health. This is an exciting time for NorthStar that warrants amplified communication and updates to our audiences. We believe there is no better way to share this information than with a highly relevant website that consistently provides streamlined, timely content."

On October 7, 2021 Cidara Therapeutics, Inc. (Nasdaq: CDTX), a biotechnology company developing long-acting therapeutics designed to improve the standard of care for patients facing serious diseases, reported that it has commenced concurrent but separate underwritten public offerings of its common stock and its Series X Convertible Preferred Stock (Press release, Cidara Therapeutics, OCT 7, 2021, View Source [SID1234636984]). With respect to the common stock offering, Cidara also expects to grant the underwriters a 30-day option to purchase additional shares of its common stock at the public offering price. The closing of each proposed offering is not contingent upon the closing of the other. The offerings are subject to market conditions, and there can be no assurance as to whether or when either or both of the offerings will be completed, or as to the actual size or terms of the offerings.

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The securities described above are being offered by Cidara pursuant to a shelf registration statement, which has been declared effective by the Securities and Exchange Commission (SEC). Preliminary prospectus supplements and the accompanying prospectus relating to the offerings will be filed with the SEC and will be available for free on the SEC’s website at View Source Copies of the preliminary prospectus supplements and accompanying prospectus relating to these offerings, when available, may be obtained from: Cantor Fitzgerald & Co., Attn: Capital Markets, 499 Park Ave., 4th Floor, New York, New York 10022, or by e-mail at [email protected].

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