On November 5, 2021 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported its financial results and development highlights for the quarter ended September 30, 2021 (Press release, Oncolytics Biotech, NOV 5, 2021, View Source [SID1234594604]). All dollar amounts are expressed in Canadian currency unless otherwise noted.

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"Over the past few months, we achieved key milestones that have advanced pelareorep’s development programs and further highlighted the advantages of its broadly applicable mechanism of action," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics Biotech Inc. "These milestones include the reporting of new clinical biomarker data from our AWARE-1 breast cancer study, which we are pleased to be announcing today. These data further demonstrate pelareorep’s immunotherapeutic effects and its ability to synergize with checkpoint inhibition. It also indicates that changes in peripheral blood T cell populations may be predictive of patient response. This exciting finding could improve our chances of success in subsequent studies by allowing for early identification of patients most likely to benefit from pelareorep therapy. We are evaluating this hypothesis as part of our BRACELET-1 breast cancer trial, which is assessing the safety, efficacy, and pharmacodynamic effects of pelareorep with and without checkpoint inhibition to support the advancement of our lead program to a registrational study."

Dr. Coffey continued, "Beyond our lead program, we also advanced our collaboration with Roche and AIO with the initiation of dosing in our phase 1/2 GOBLET trial. This trial addresses a pressing unmet need in gastrointestinal cancer by leveraging pelareorep’s immunotherapeutic effects to overcome checkpoint inhibitor resistance and then increase the proportion of patients responding to checkpoint inhibition therapies. Looking forward, we will continue to strategically leverage collaborations and partnerships to drive pelareorep’s development as an enabling technology for various immuno-oncology agents across multiple indications with high unmet needs. We believe this will allow us to maximally benefit from pelareorep’s value-creating potential while maintaining focus on our lead breast cancer program."

Third Quarter and Subsequent Highlights

Breast Cancer Program

AWARE-1 data indicate that changes in peripheral blood T cell populations may be a predictive biomarker of pelareorep therapy

Additional analyses from AWARE-1’s first two cohorts being announced today focus on changes in the peripheral blood and tumors’ T cell populations of HR+/HER2- early-stage breast cancer patients following treatment with pelareorep and letrozole without (cohort 1) or with (cohort 2) the PD-L1 inhibitor atezolizumab. These changes were compared to assessments of CelTIL score (a measure of tumor cellularity and inflammation) and tumor-infiltrating CD8+ T cells, two metrics that are associated with favorable clinical outcomes. Highlights from the analyses using Spearman’s Rank-Order Correlation not adjusted for multiplicity are shown below:

Pooled analysis across cohorts showed:
A statistically significant decrease in peripheral blood T cell diversity post-treatment, explained by the expansion and generation of new middle frequency anti-viral and anti-tumor T cell clones.
A statistically significant association between pre- vs. post-treatment decreases in peripheral blood T cell diversity and increased post-treatment CelTIL score.
A statistically significant association between increased peripheral blood T cell fraction pre-treatment and tumor-infiltrating CD8+ T cells post-treatment.
Comparative analysis of cohort 1 vs. cohort 2 showed:
The addition of atezolizumab enhanced pelareorep’s ability to generate and expand new anti-viral and anti-tumor T cell clones.
A greater decrease in pre- vs. post-treatment changes in peripheral blood T cell diversity in cohort 2 compared to cohort 1.
A numerical association between decreased post-treatment T cell diversity in the peripheral blood and pre- vs. post-treatment increases in tumor-infiltrating CD8+ T cells in cohort 1. This association reached statistical significance in cohort 2 with the addition of atezolizumab.
Collectively, these analyses further demonstrate pelareorep’s immunotherapeutic mechanism of action and its ability to synergize with checkpoint inhibitors such as atezolizumab. They also suggest that changes in peripheral blood T cell populations are predictive of response to pelareorep therapy and could potentially serve as the basis for a blood-based biomarker to inform the design of subsequent studies.

Oncolytics has completed its planned analyses of AWARE-1’s first two cohorts, which enrolled patients with HR+/HER2- breast cancer. Evaluation of these cohorts was the core objective of AWARE-1, as HR+/HER2- is the breast cancer subtype Oncolytics intends to examine in a future registrational study. Following the completion of these cohorts, Oncolytics amended the protocol of the trial so that all remaining cohorts focus exclusively on patients with the HER2+ breast cancer subtype. Together with AWARE-1’s first two cohorts and the ongoing IRENE trial in triple-negative breast cancer, these cohorts will facilitate the evaluation of pelareorep in all breast cancer subtypes.

Partner Adlai Nortye dosed first patient in Chinese bridging trial evaluating pelareorep-paclitaxel combination treatment in breast cancer

The bridging clinical trial is evaluating the safety, tolerability, and preliminary efficacy of pelareorep-paclitaxel combination therapy in Chinese patients with advanced or metastatic breast cancer. Results are expected to allow Adlai Nortye to include data from Oncolytics’ North American IND-213 and BRACELET-1 trials in a future submission to Chinese regulators. This may accelerate pelareorep’s clinical development path in China, which has a rapidly growing pharmaceutical market that is currently the second largest in the world.

Gastrointestinal Cancers Program

Dosed first patient in the phase 1/2 GOBLET trial in collaboration with Roche and AIO

GOBLET is a phase 1/2 multi-center trial designed to evaluate the use of pelareorep in combination with Roche’s anti-PD-L1 checkpoint inhibitor atezolizumab in patients with metastatic pancreatic, metastatic colorectal, and advanced anal cancers. The trial is being managed by AIO, a leading academic cooperative medical oncology group based in Germany. In addition to evaluating the safety and efficacy of pelareorep-atezolizumab treatment, the trial also seeks to validate CEACAM6 and T cell clonality as predictive biomarkers, which may improve the patient selection process in future registration studies and increase their likelihood of success. The trial builds off previously reported phase 2 data demonstrating clinical proof-of-concept for pelareorep-checkpoint inhibitor combination therapy in pancreatic cancer (link to PR, link to poster), as well as prior early clinical data showing that pelareorep-based combinations stimulated an adaptive immune response and led to a greater than 90% clinical benefit rate in KRAS mutated colorectal cancer patients (link to PR, link to study), and a greater than 80% increase in progression-free survival in pancreatic cancer patients with low levels of CEACAM6 expression (link to PR, link to poster).

Additional Immunotherapeutic Combinations and Opportunities

Announced preclinical data demonstrating the synergistic immunotherapeutic effects of pelareorep combined with radiotherapy

Preclinical data presented in a poster at The International Conference on Immunotherapy Radiotherapy Combinations showed that combination treatment with pelareorep and radiotherapy promoted the tumor infiltration of anti-cancer T cells and prolonged survival in a murine cancer model. Increased infiltration of anti-cancer T cells was observed both in tumors exposed to local treatment with radiation and pelareorep, and in tumors located away from the treatment site. Collectively, these data are indicative of the synergistic immunotherapeutic effects of the pelareorep-radiotherapy combination (link to PR, link to poster).

Financial Highlights

As of September 30, 2021, the Company reported $48.1 million in cash and cash equivalents.
Operating expense for the third quarter of 2021 was $2.9 million, compared to $2.5 million in the third quarter of 2020.
R&D expense for the third quarter of 2021 was $3.3 million, compared to $3.9 million in the third quarter of 2020.
Net cash used in operating activities for the third quarter of 2021 was $3.7 million, compared to $6.1 million for the third quarter of 2020.
The net loss for the third quarter of 2021 was $4.9 million, compared to a net loss of $6.7 million in the third quarter of 2020. The basic and diluted loss per share was $0.09 in the third quarter of 2021, compared to a basic and diluted loss per share of $0.16 in the third quarter of 2020.
Anticipated Milestones and Catalysts

Completion of enrollment in phase 2 BRACELET-1 metastatic breast cancer study: Q4 2021/Q1 2022
Interim safety update from phase 2 IRENE study in triple-negative breast cancer: Q4 2021
Multiple myeloma study data: Q4 2021
Oncolytics expects to provide updates on the timing of the following milestones:

Interim safety update from BRACELET-1 metastatic breast cancer study
Phase 2 BRACELET-1 metastatic breast cancer study: final data
Webcast and Conference Call
Management will host a conference call for analysts and institutional investors at 8:00 a.m. ET today, November 5, 2021. To access the call, please dial (888) 664-6383 (North America) or (416) 764-8650 (International) and, if needed, provide confirmation number 7285-9440. A live webcast of the call will also be available by clicking here or on the Investor Relations page of Oncolytics’ website (LINK) and will be archived for three months. A dial-in replay will be available for one week and can be accessed by dialing (888) 390-0541 (North America) or (416) 764-8677 (International) and using replay code: 859-440#.

On November 5, 2021 Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, reported that it will present new data demonstrating clinical and preclinical activity of its selective CDK8/19 inhibitor RVU120 (SEL120) and its selective PIM/FLT3 inhibitor SEL24 (MEN1703) during the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, being held on December 11 – December 14, 2021, in Atlanta and at the 44th Annual San Antonio Breast Cancer Symposium (SABCS) being held on December 7 – December 10, 2021 (Press release, Ryvu Therapeutics, NOV 5, 2021, View Source;collaborators-to-present-clinical-and-translational-data-from-rvu120-and-sel24men1703-at-the-63rd-ash-annual-meeting–exposition-and-the-44th-annual-sabcs-301416881.html [SID1234594621]).

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An acceptable safety profile and early signs of efficacy will be presented for RVU120, a selective CDK8/19 inhibitor being developed in hematologic and solid tumors, in the first-in-human (FIH) Phase Ib dose-escalation trial (CLI120-001) currently ongoing in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS). The preliminary signs of efficacy for RVU120 include a Complete Response (CR) in an AML patient and an erythroid response (ER) in a HR-MDS patient who had relapsed after several lines of previous treatment.

Translational research will be presented that potentially links the clinical response in an AML patient to DNMT3A-mutations via evidence in DNMT3A-mutated AML patient-derived cells (PDCs). Further translational research shows evidence that the clinical erythroid response in an MDS patient is potentially a result of strong erythroid differentiation potential of RVU120 in preclinical models. Enrollment is ongoing in cohort 4 at seven clinical sites in the US and Europe to gather additional safety data in the study.

An additional poster on the potential efficacy of RVU120 in hormone-negative breast cancer models will be presented at the 2021 San Antonio Breast Cancer Symposium.

Ryvu licensee Menarini Group will be presenting SEL24/MEN1703 data from the First-in-Human, Dose Escalation (DE) and Cohort Expansion (CE) CLI24-001 trial (DIAMOND-01, ClinicalTrials.gov identifier: NCT03008187).

"We are excited to present data from our ongoing Phase Ib dose escalation study of RVU120 in AML and HR-MDS, where we have seen clinical responses, and in solid tumors with strong translational data in breast cancer," said Pawel Przewiezlikowski, Chief Executive Officer at Ryvu Therapeutics. "It is a true milestone for Ryvu and our collaborators from MD Anderson Cancer Center and Menarini to have six posters accepted for presentation on RVU120 and SEL24."

The abstracts accepted for poster presentation at the 63rd ASH (Free ASH Whitepaper) Annual Meeting & Exposition include:

CLI120-001 Phase Ib Study of RVU120 (SEL120) in Patients with AML and High-Risk MDS: Updated Safety/Efficacy Results from Initial Dose Escalation (Publication Number: 3418), Camille Abboud Sr., MD (Washington University in Saint Louis/ Washington University School of Medicine) et al.

Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III
Date: Monday, December 13, 2021
Presentation Time: 6:00 PM – 8:00 PM
RVU120 (SEL120) CDK8/19 Inhibitor – a Drug Candidate for the Treatment of MDS Can Induce Erythroid Differentiation (Publication Number: 1518), Tomasz Rzymski, Ph.D. (Ryvu Therapeutics) et al.

Session Name: 636. Myelodysplastic Syndromes—Basic and Translational: Poster I
Date: Saturday, December 11, 2021
Presentation Time: 5:30 PM – 7:30 PM
Inhibition of Cyclin Dependent Kinase 8 (CDK8): A Novel Approach to Target the Leukemia Initiating Cells (LICs) in T-Cell Acute Lymphoblastic Leukemia (T-ALL) (Publication Number: 2250), Sujan Piya, Ph.D. (MD Anderson Cancer Center) et al.

Session Name: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II
Date: Sunday, December 12, 2021
Presentation Time: 6:00 PM – 8:00 PM
Preclinical and Clinical Signs of Efficacy of RVU120 (SEL120), a Specific CDK8/19 Inhibitor in DNMT3A-Mutated AML (Publication Number: 2371), Tomasz Rzymski, Ph.D. (Ryvu Therapeutics) et al.

Session Name: 617. Acute Myeloid Leukemias: Biomarkers, Molecular Markers and Minimal Residual Disease in Diagnosis and Prognosis: Poster II
Date: Sunday, December 12, 2021
Presentation Time: 6:00 PM – 8:00 PM
SEL24(MEN1703) Inhibits PIM/FLT3 Downstream Target in Acute Myeloid Leukemia (AML) Patients: Results of the Pharmacodynamics (PD) Assay and Genomic Profiling in the First-in-Human Diamond-01 Trial (Publication Number: 3436), Alessandro Paoli (Menarini Group) et al.

Session Name: 617. Acute Myeloid Leukemias: Biomarkers, Molecular Markers and Minimal Residual Disease in Diagnosis and Prognosis: Poster III
Date: Monday, December 13, 2021
Presentation Time: 6:00 PM – 8:00 PM
All of the abovementioned abstracts are available on-line at: View Source

The abstract accepted for the poster presentation at the 2021 San Antonio Breast Cancer Symposium, taking place on December 7-10, 2021, at Henry B. Gonzalez Convention Centre in San Antonio, Texas:

Selective CDK8/CDK19 inhibitor RVU120 demonstrates efficacy against hormone-independent breast cancer cells in vitro and in vivo (#1766), Tomasz Rzymski, Ph.D. (Ryvu Therapeutics) et al.

Program Number: P5-17-13
Poster Session 5: December 10, 2021: 7:00 AM – 8:30 AM

On November 5, 2021 PerkinElmer, Inc. (NYSE: PKI), a global leader committed to innovating for a healthier world, reported that the Company will present at the virtual 2021 Stifel Healthcare Conference on Tuesday, November 16, 2021 at 8:40 a.m. ET (Press release, PerkinElmer, NOV 5, 2021, View Source [SID1234594590]).

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Jamey Mock, senior vice president and chief financial officer of PerkinElmer, will provide an update on the Company and its strategic priorities. To register, click here.

A live audio webcast will be available on the Investors section of the Company’s website at www.perkinelmer.com. A replay of the presentation will be posted on the PerkinElmer website after the event and will be available for 90 days following.

On November 5, 2021 Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing innovative medicines based on cancer cell biology, reported dosing of the first patient in the Company’s multi-cohort Phase 1/2 study of oral fadraciclib in patients with leukemias or myelodysplastic syndromes (MDS) (Press release, Cyclacel, NOV 5, 2021, View Source [SID1234594605]).

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"We are proud to have achieved this second key clinical milestone and corporate objective following the start of the oral fadraciclib Phase 1/2 solid tumor and lymphoma study last quarter," said Spiro Rombotis, Cyclacel’s President and Chief Executive Officer. "After opening these two streamlined, registration-directed Phase 1/2 studies with fadraciclib as planned, we will next evaluate the clinical potential of oral CYC140, our PLK1 inhibitor, first in solid tumors and lymphomas and then in leukemias. We look forward to providing periodic updates on our clinical progress and data from these open-label studies when available."

"We are pleased to have dosed the first patient in this leukemia study and are delighted by the enthusiasm and strong interest from current and prospective investigators," said Mark Kirschbaum M.D., Senior Vice President and Chief Medical Officer of Cyclacel. "The study has initially opened at City of Hope, a world-renowned cancer research and treatment organization, with more sites to join later. We are building a distinguished, global network of participating institutions for this leukemia study, the ongoing solid tumor clinical study and also for preclinical collaborations. We are excited to begin this second mid-stage study of fadraciclib with the objective of registration-enabling outcomes as a single agent and in relevant combinations, potentially offering a new treatment option for patients with leukemias, MDS and related disorders."

"Based upon the mechanism of action and prior clinical activity shown to date, further exploration of this novel CDK2/9 inhibitor, both as a single-agent and in combinations, is warranted across a number of leukemias and MDS," said Brian Ball, M.D., Assistant Professor, Department of Hematology and Hematopoietic Cell Transplantation at City of Hope. "We look forward to enrolling patients in this trial, performing correlative studies, and evaluating potential treatment benefit for this experimental therapy, particularly in novel subsets of AML, which we have recently described and which may respond to inhibition of these targets."

The Phase 1/2 registration-directed trial, designated CYC065-102, uses a streamlined design and will first determine the recommended Phase 2 dose (RP2D) for single-agent, oral fadraciclib. Once RP2D has been established, the trial will immediately enter into proof-of-concept, cohort stage, using a Simon 2-stage design, where fadraciclib, both as a single agent and in combinations, will be administered to patients in up to seven cohorts relevant to the drug’s mechanism of action and informed by the clinical activity of fadraciclib in previous studies.

Single-agent cohorts will include patients with acute myeloid leukemia (AML) or MDS who have an inadequate response or have progressed on venetoclax combinations with hypomethylating agent (HMA) or low dose Ara C; relapsed/refractory AML or MDS patients with FLT3, KIT or MAPK pathways (including N and K RAS, BRAF, PTPN11, NF1). The trial will also include patients with chronic lymphocytic leukemia (CLL) who have progressed after at least two lines of therapy including a BTK inhibitor and venetoclax.

Combination cohorts for patients with AML or MDS are: fadraciclib and azacitidine for patients with AML or MDS who progressed with hypomethylating (HMA) treatments and also fadraciclib and venetoclax for patients that have progressed after venetoclax therapy. A further combination cohort of fadraciclib and venetoclax will enroll patients with CLL or small lymphocytic lymphoma (SLL) who have progressed after venetoclax therapy. An additional basket cohort will evaluate patients with biomarkers relevant to the drug’s mechanism, including MCL1 and MYC.

The protocol allows for expansion of a cohort based on response which may allow acceleration of the clinical development and registration plan for fadraciclib.

About Cyclin-Dependent Kinases and Fadraciclib

Cyclin-dependent kinases (CDKs) are critical for cell cycle control and transcriptional regulation. Dysregulated CDKs have been linked to the cancer hallmarks of uncontrolled proliferation and increased cancer cell survival. Fadraciclib, a next generation CDK inhibitor, is a highly selective, potent, orally and intravenously available, inhibitor of CDK2 and CDK9. CDK2 drives cell cycle transitions and CDK9 regulates transcription of genes through phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II (RNAP II). By inhibiting CDK2 and CDK9 fadraciclib causes apoptotic death of cancer cells at sub-micromolar concentrations. Published data support the hypothesis that concomitant inhibition of CDK2 and CDK9 yields synergistic anti-tumor activity rather than inhibition of CDK2 or CDK9 alone.

Preclinical and animal model data suggest that fadraciclib may benefit patients with adult and pediatric hematological malignancies, such as ALL, AML, B-cell lymphoma, CLL, and multiple myeloma and certain cyclin E-addicted or MYC-amplified solid tumors, including certain forms of breast cancer, neuroblastoma, ovarian cancer and uterine serous carcinoma. Similarly to FDA-approved CDK4/6 inhibitors, fadraciclib may be useful in combination with other anticancer drugs, including HER2 inhibitors, such as trastuzumab, or BCL2 inhibitors, such as venetoclax.

Venetoclax has modest single-agent activity in AML. MCL1 dependence appears to correlate with resistance to venetoclax. A pre-clinical study confirmed synergy of fadraciclib and venetoclax, suggesting that the suppression of both BCL2 and MCL1 may be more beneficial than inhibiting either protein alone.

Pre-existing or emergent mutations in the MAPK pathway contribute towards resistance to venetoclax, FLT3 inhibitors and mutant IDH inhibitors. These mutations are also frequent in proliferative CMML progressing to AML. Activating mutations in the MAPK pathway upregulates MCL1 and renders AML resistant to apoptosis. CDK9 inhibition downregulates MCL1 transcriptionally and can potentially be effective in the context of MAPK and other receptor tyrosine kinase mutations.

In a prior Phase 1 open-label trial (CYC065-01), patients with high copy CCNE (cyclin E), MYC or MCL1 showed sensitivity to intravenously-administered, single-agent fadraciclib. A heavily pretreated patient with MCL1 amplified endometrial cancer achieved a radiographically confirmed partial response (PR) after a month and a half on fadraciclib. This patient continues on therapy for almost two years and reduction in her target tumor lesions has reached 100%. An additional patient with cyclin E amplified ovarian cancer achieved stable disease with 29% shrinkage in her target tumor lesions.

References: Do, KT, et al., 32nd EORTC/AACR/NCI Virtual Symposium 24-25 Oct. 2020; Frame S et al, PLOS One, 2020; Frame et al, AACR (Free AACR Whitepaper), 2010, Abs 3886; Poon E et al, JCI 2020; Scaltriti M et al, PNAS, 2011.

On November 5, 2021 Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX), a clinical-stage pharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for rare endocrine diseases and endocrine-related tumors, reported financial results for the third quarter ended September 30, 2021 and provided a corporate update (Press release, Crinetics Pharmaceuticals, NOV 5, 2021, View Source [SID1234594591]).

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"Positive Phase 1 readouts from our CRN04894 and CRN04777 programs during the third quarter have us advancing a diverse pipeline that includes three wholly-owned new chemical entities (NCEs) with clinical proof-of-concept," said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. "The drug development blueprint followed by these NCEs, which aims for early de-risking through animal and healthy volunteer studies leveraging well-established endocrine biomarkers, is now being applied to our recently unveiled parathyroid hormone receptor antagonist program and other discovery efforts. We also continue to make strong progress in our efforts to develop paltusotine as an oral treatment for acromegaly and neuroendocrine tumors complicated by carcinoid syndrome. With a strong financial foundation that was recently bolstered by our successful common stock offering, we believe we are well positioned to advance our pipeline programs and achieve a regular cadence of milestones."

Dr. Struthers continued, "Beyond our internal pipeline, our drug discovery platform has also generated exciting radiopharmaceutical candidates with the potential to treat a broad range of cancers. This led us to co-found Radionetics Oncology, which has positioned Crinetics to participate in the value of these assets while maintaining focus on our core mission of delivering much-needed therapies to patients with endocrine diseases."

THIRD QUARTER AND SUBSEQUENT HIGHLIGHTS
Reported positive data from single-ascending dose (SAD) cohorts of first-in-human study of CRN04777. In September 2021, Crinetics announced preliminary data from the SAD cohorts of an ongoing Phase 1 study of CRN04777, its somatostatin receptor type 5 (SST5) agonist being developed as a treatment for congenital hyperinsulinism. The data provided evidence of clinically meaningful suppression of insulin secretion by showing dose-dependent reductions in glucose-stimulated insulin secretion and a dose-dependent reversal of sulfonylurea-induced insulin secretion in a pharmacologic model of congenital hyperinsulinism. In addition, the data suggest CRN04777 was orally bioavailable and demonstrated dose-proportional pharmacokinetics. Single doses of CRN04777 were well tolerated, as all adverse events were considered mild/moderate. Data from multiple-ascending dose (MAD) cohorts of the Phase 1 study are expected in the first quarter of 2022.
Reported positive data from SAD cohorts of first-in-human study of CRN04894. In August 2021, Crinetics announced preliminary data from the SAD cohorts of an ongoing Phase 1 study of CRN04894, its adrenocorticotropic hormone (ACTH) antagonist being developed as a treatment for diseases of ACTH excess. The data provided evidence of clinically relevant cortisol suppression and showed dose-dependent reductions in basal cortisol levels as well as suppression of cortisol following ACTH challenge. In addition, the data suggest that CRN04894 was orally bioavailable and demonstrated dose-proportional pharmacokinetics. Single doses of CRN04894 were well-tolerated, as all adverse events were considered mild. Data from the MAD cohorts of the Phase 1 study are expected in the first quarter of 2022.
Unveiled its parathyroid hormone receptor antagonist program. In September 2021, Crinetics announced its intent to develop a nonpeptide oral parathyroid hormone (PTH) receptor antagonist for the treatment of hypercalcemia associated with hyperparathyroidism (HPT) and other diseases of PTH receptor type 1 (PTHR1) over-activation. Details on the preclinical efforts supporting the program were presented in a late-breaking poster at the annual meeting of the American Society for Bone and Mineral Research (ASBMR). More information on the program and a copy of the poster can be found here.
Co-founded Radionetics Oncology. In October 2021, Crinetics, together with 5AM Ventures and Frazier Healthcare Partners, founded Radionetics Oncology, an independently operated company that aims to develop a deep pipeline of novel, targeted, nonpeptide radiopharmaceuticals for the treatment of a broad range of oncology indications. In conjunction with formation of the company, Radionetics received an exclusive world-wide license to a radiotherapeutics technology platform and intellectual property from Crinetics in exchange for equity, milestones in excess of $1 billion and single-digit royalties on net sales. Radionetics launched with a $30 million private financing with 5AM Ventures and Frazier Healthcare Partners as the sole investors.
Strengthened balance sheet with successful common stock offerings. In July 2021, Crinetics entered into a securities purchase agreement with Frazier Healthcare Partners for the private placement of 851,306 shares at $17.62 per share, raising gross proceeds of $15.0 million. In October 2021, Crinetics completed an underwritten public offering of 8,712,400 shares of its common stock at a price to the public of $19.80 per share, raising gross proceeds of $172.5 million.
THIRD QUARTER 2021 FINANCIAL RESULTS
Research and development expenses were $21.6 million for the three months ended September 30, 2021, compared to $13.7 million for the same period in 2020. The increase was primarily attributable to increased spending on manufacturing and development activities of $4.3 million associated with our clinical and nonclinical activities for paltusotine and our other clinical and preclinical programs, and an increase in personnel costs of $3.2 million, of which stock-based compensation was $1.2 million.
General and administrative expenses were $6.2 million for the three months ended September 30, 2021, compared to $4.8 million for the same period in 2020. The increase was primarily due to additional personnel costs of $1.0 million, of which stock-based compensation was $0.6 million.
Net loss for the three months ended September 30, 2021, was $27.9 million, compared to a net loss of $18.3 million for the three months ended September 30, 2020.
Unrestricted cash, cash equivalents and investments totaled $193.3 million as of September 30, 2021, compared to $170.9 million as of December 31, 2020. The $193.3 million in unrestricted cash, cash equivalents and investments does not include the $172.5 million in gross proceeds from the Company’s October 2021 common stock offering.
As of October 31, 2021, the company had 47,499,886 common shares outstanding.