On May 8, 2023 Sana Biotechnology, Inc. (NASDAQ: SANA), a company focused on changing the possible for patients through engineered cells, reported financial results and business highlights for the first quarter 2023 (Press release, Sana Biotechnology, MAY 8, 2023, View Source [SID1234631177]).

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"Our initial human studies using Sana’s hypoimmune technology remain on track, as we have begun enrolling patients in our SC291 trial and expect to deliver data from two clinical studies in 2023," said Steve Harr, Sana’s President and Chief Executive Officer. "We are also making progress in our earlier-stage pipeline and are on pace to file two additional INDs later this year and potentially three more in 2024. The quality of our key hires, publications in high quality peer-reviewed journals, and presentations at important scientific conferences are recent validations of the science behind Sana’s programs. Our capital position and people give us the resources for multiple data read-outs with our current balance sheet, and we continue to be optimistic about our future, with the opportunity to see the potential of these medicines in patients starting this year."

Recent Corporate Highlights

Opportunity for clinical proof of concept for two different first-in-human studies, each with the potential for initial clinical data this year

SC291 is an ex vivo hypoimmune-modified CD19-directed allogeneic CAR T cell therapy. The goal of the hypoimmune platform is to overcome the immunologic rejection of allogeneic cells, which, if successful with SC291, may result in longer CAR T cell persistence and a higher rate of durable complete responses for patients with B-cell malignancies.
Received clearance from the Food and Drug Administration (FDA) to initiate a first-in-human Phase 1 study of SC291 in patients with B-cell malignancies (ARDENT).
Began enrollment in the ARDENT Phase 1 study.
Granted Fast Track Designation for SC291 by the FDA for the treatment of relapsed/refractory (r/r) large B-cell lymphoma and r/r chronic lymphocytic leukemia.
SC291 has the potential to serve as clinical proof-of-platform for other hypoimmune-modified CAR T cell candidates using validated CAR constructs in development at Sana for hematological malignancies, such as SC262 (CD22) and SC255 (BCMA). Sana’s goal is to file INDs for SC262 later this year and SC255 in 2024.
Sana is developing SC451, a hypoimmune-modified stem-cell derived islet cell therapy for patients with type 1 diabetes. SC451, which is engineered with Sana’s hypoimmune technology, has the potential to replace missing islet cells without immunosuppression in persons with type 1 diabetes by evading allogeneic and autoimmune responses.
Expect initial data later this year from an investigator-sponsored trial transplanting hypoimmune-modified primary human islet cells into type 1 diabetes patients. The goal of the study is to show cell survival and immune evasion without the need for any immunosuppression.
Sana’s goal is to file an IND for SC451 in 2024.
Published preclinical data in Nature Communications describing immune evasion, persistence, and durable anti-tumor activity of Sana’s hypoimmune-modified CD19-directed CAR T cells

Sana developed hypoimmune-modified CD19 targeted allogeneic CAR T cells and compared them to unmodified CD19-targeted allogeneic CAR T cells in a murine leukemia model with a humanized immune system.
Although both hypoimmune-modified and unmodified CAR T cells showed robust early tumor killing, cell durability was much greater in humanized mice treated with hypoimmune-modified cells. Hypoimmune-modified allogeneic CAR T cells persisted and removed all evidence of tumor for the duration of the study. Hypoimmune-modified CAR T cells also cleared all evidence of tumor after re-injection with cancer cells 90 days into the study. In contrast and consistent with the experience in patients to date, unmodified allogeneic CAR T cells show greatly reduced persistence and a high rate of tumor recurrence in this model.
These studies provide additional insight for SC291 and the allogeneic hypoimmune CAR T platform more broadly, including SC262 and SC255.
Published preclinical data in Science Translational Medicine demonstrating that Sana’s hypoimmune-modified pseudo-islets control type 1 diabetes

Sana developed hypoimmune-modified human islet cells, which cluster into effective endocrine organoids termed "pseudo islets" (p-islets) and studied these p-islets in multiple preclinical models.
Preclinical data showed that p-islets survive, persist, escape allogeneic rejection, and normalize blood glucose in diabetic models with humanized immune systems.
Two different murine models showed that the hypoimmune-modified cells can evade autoimmune rejection and normalize blood glucose. First, these cells were studied in the NOD mouse model, which is the standard model for autoimmunity in diabetes. Second, Sana created a humanized mouse model with immune cells from a diabetic person and transplanted pancreatic islet cells derived from the diabetic person’s stem cells. In both cases, unmodified pancreatic islet cells were rapidly cleared by the immune system. In contrast, hypoimmune-modified pancreatic islet cells survived, persisted, and provided sustained blood glucose control in both models.
These studies provide additional insight for SC451 in persons with type 1 diabetes.
Published preclinical data in Nature Biotechnology demonstrating that Sana’s hypoimmune-modified cells survive allogeneic transplant across several species, including non-human primates (NHPs) with normal immune systems, and remain fully functional

Sana developed hypoimmune-modified NHP induced pluripotent stem cells (iPSCs) and transplanted them into immune-competent NHPs. Results were compared to transplantation of unmodified iPSCs into immune-competent NHPs.
Data showed that hypoimmune-modified iPSCs survived for the duration of the study (16 weeks), while unmodified iPSCs disappeared within two weeks. There was an antibody and T cell response directed toward unmodified cells, but not hypoimmune-modified cells.
Hypoimmune-modified primary NHP pancreatic islet cells survived 40 weeks (duration of the study) after allogeneic transplantation into an immune-competent NHP versus less than one week for unmodified primary islet cells.
Hypoimmune-modified iPSCs were differentiated into pancreatic islet cells. Transplantation of hypoimmune-modified iPSC-derived pancreatic cells into allogeneic diabetic mice with a humanized immune system showed immune evasion after transplantation for the duration of the studies (4 weeks) and amelioration of diabetes and normalization of blood glucose levels.
Presented multiple abstracts at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting highlighting ex vivo hypoimmune-modified allogeneic CAR T cells, as well as in vivo cell-specific delivery of genetic material using Sana’s in vivo fusogen platform

Presented preclinical data demonstrating that hypoimmune-modified CAR T cells provide lasting tumor control in immunocompetent allogeneic humanized mice even with tumor re-challenge.
Presented preclinical data in a late-breaking poster presentation demonstrating that the increased potency of CD8-targeted fusosomes enhances CAR transgene delivery to resting primary T cells.
Presented preclinical data demonstrating the effectiveness of Sana’s fully human CD19 CAR delivered by CD8-targeted fusosomes in tumor killing assays. These fusosomes led to similar levels of tumor control as ex vivo generated CD19 CAR T cells.
Presented preclinical data demonstrating increased potency of CD8-targeted fusosomes delivering a CD19 CAR with pre-treatment of resting T cells with IL-7, rapamycin, or both. Pre-treatment with these molecules led to increased anti-tumor efficacy through increased T cell transduction and greater CAR T cell expansion.
Strengthened Research and Development leadership with the appointment of two seasoned drug developers

Appointed Doug Williams, Ph.D., as President of Research and Development. Dr. Williams has over 30 years of experience leading R&D organizations – including at Biogen, Seattle Genetics (now Seagen), Amgen, and Immunex – and over the course of his career has participated in the development of over a dozen approved drugs including multiple blockbusters.
Appointed Gary Meininger, M.D., as Chief Medical Officer. Dr. Meininger has approximately 20 years of experience in drug development. Most recently, he was at Vertex as Senior Vice President, Head of Clinical Development for Vertex Cell and Genetic Therapies and previously was at Janssen and Merck. Dr. Meininger is currently the industry representative to the FDA’s Endocrine and Metabolic Drug Advisory Committee.
First Quarter 2023 Financial Results

GAAP Results

Cash Position: Cash, cash equivalents, and marketable securities as of March 31, 2023 were $355.1 million compared to $434.0 million as of December 31, 2022. The decrease of $78.9 million was primarily driven by cash used in operations of $79.2 million and cash used for the purchase of property and equipment of $2.2 million. Cash used in operations includes multiple cash payments that will not recur this year. In addition, our cash balance will increase by $6.1 million in July 2023 as the letter of credit related to the Fremont facility reduces from $6.7 million to $0.6 million in July 2023.

Research and Development Expenses: For the three months ended March 31, 2023, research and development expenses, inclusive of non-cash expenses, were $67.2 million compared to $72.7 for the same period in 2022. The decrease of $5.5 million was primarily due to a decline in costs to acquire technology, laboratory supplies, third-party manufacturing costs, and other research costs. These decreases were partially offset by increased clinical development costs, personnel-related costs, operating costs for our manufacturing facility in Bothell, Washington, and other allocated costs. Research and development expenses include non-cash stock-based compensation of $6.0 million and $5.7 million, for the three months ended March 31, 2023 and 2022, respectively.

Research and Development Related Success Payments and Contingent Consideration: For the three months ended March 31, 2023, we recognized an expense of $0.1 million and a gain of $55.4 million for the same period in 2022, in connection with the change in the estimated fair value of the success payment liabilities and contingent consideration in aggregate. The value of these potential liabilities may fluctuate significantly with changes in Sana’s market capitalization and stock price.

General and Administrative Expenses: General and administrative expenses for the three months ended March 31, 2023, inclusive of non-cash expenses, were $16.8 million compared to $14.4 million for the same period in 2022. The increase of $2.4 million was primarily due to operating costs for the previously planned manufacturing facility, formerly in research and development expense, and increased non-cash stock-based compensation and personnel-related expenses. General and administrative expenses include non-cash stock-based compensation of $2.8 million and $2.0 million, for the three months ended March 31, 2023 and 2022, respectively.

Net Loss: Net loss for the three months ended March 31, 2023 was $82.1 million, or $0.43 per share, compared to $31.4 million, or $0.17 per share, for the same period in 2022.
Non-GAAP Measures

Non-GAAP Operating Cash Burn: Non-GAAP operating cash burn for the three months ended March 31, 2023 was $74.8 million compared to $82.0 million for the same period in 2022. Non-GAAP operating cash burn is the decrease in cash, cash equivalents, and marketable securities, excluding cash inflows from financing activities, cash outflows from business development and non-recurring restructuring activities, and the purchase of property and equipment.

Non-GAAP Net Loss: Non-GAAP net loss for the three months ended March 31, 2023 was $82.0 million, or $0.43 per share, compared to $86.9 million, or $0.47 per share, for the same period in 2022. Non-GAAP net loss excludes non-cash expenses related to the change in the estimated fair value of contingent consideration and success payment liabilities.
A discussion of non-GAAP measures, including a reconciliation of GAAP and non-GAAP measures, is presented below under "Non-GAAP Financial Measures."

On May 8, 2023 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for RAS-addicted cancers, reported its financial results for the quarter ended March 31, 2023, and provided an update on corporate progress (Press release, Revolution Medicines, MAY 8, 2023, View Source [SID1234631176]).

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"Revolution Medicines is off to a strong start in 2023 by reporting encouraging preliminary findings of antitumor activity and safety/tolerability in our Phase 1/1b study of RMC-6236, a first-in-class RASMULTI(ON) inhibitor," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "The promising early clinical data we shared in our February earnings update serve as important initial validation of the drug candidate’s novel mechanism of action and potential clinical utility for treating a range of RAS-addicted cancers. We also view these data as platform validation with positive implications across our deep and pioneering portfolio of RAS(ON) Inhibitors.

"Our successful public equity offering in March raised gross proceeds of $345 million, reinforcing our financial position and enabling us to consider additional near-term and longer-term investments to strengthen clinical advancement of our first wave of RAS(ON) Inhibitors. We are continuing dose-escalation of RMC-6236 and RMC-6291 and working to bring RMC-9805 into the clinic. We are also laying the groundwork for advanced development of RMC-6236 by strengthening senior leadership across late-stage development, manufacturing, and commercial planning and expanding clinical supply to enable seamless program progression."

Clinical and Development Highlights

RAS(ON) Inhibitors

RMC-6236 (RASMULTI)
RMC-6236 is an oral, selective, first-in-class RAS(ON) Inhibitor designed to treat patients with cancers driven by a wide range of common RAS mutations. Initially being evaluated as monotherapy, it may also be deployed as a RAS Companion Inhibitor in combination with mutant-selective RAS(ON) Inhibitors and in other combination treatment strategies.

The company presented early findings from its Phase 1/1b monotherapy trial (NCT05379985) during its Q4 earnings call. This multicenter, open-label, dose-escalation and dose-expansion study is evaluating RMC-6236 in patients with advanced solid tumors harboring KRASG12X mutations. The data provide preliminary, promising evidence of anti-tumor activity at generally well tolerated dose levels. A maximum tolerated dose and recommended Phase 2 dose have not yet been reached and dose escalation above 160 mg per day dose is ongoing.

The company currently plans to provide further evidence of first-in-class single agent activity from the ongoing study in mid-2023, with multiple updates this year through a combination of corporate and scientific meeting presentations beginning in Q3.
RMC-6291 (KRASG12C)
RMC-6291, an oral, selective, covalent inhibitor of KRASG12C(ON) designed to treat patients with cancers driven by the KRASG12C mutant, is the first of the company’s mutant-selective RAS(ON) Inhibitors to enter clinical development and the first reported clinical-stage inhibitor of KRASG12C that uses a highly differentiated mechanism of action.

The ongoing Phase 1/1b monotherapy trial (NCT05462717) is a multicenter, open-label, dose-escalation and dose-expansion study of RMC-6291 in patients with advanced KRASG12C mutant solid tumors. Early findings have shown that RMC-6291 is orally bioavailable, has exhibited pharmacokinetics consistent with preclinical findings, is generally well tolerated and is in a pharmacologically active range.

In April 2023, RMC-6291 was featured in the "New Drugs on the Horizon" session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2023 Annual Meeting. The presentation provided the first disclosure of its chemical structure and demonstrated that RMC-6291 drove deep and durable tumor regressions in a preclinical model of NSCLC brain metastasis.

The company currently plans to provide a preliminary report of the clinical profile for RMC-6291 in the second half of 2023.
RMC-9805 (KRASG12D)
RMC-9805 is an oral, selective, covalent inhibitor of KRASG12D(ON), the most common driver of RAS-addicted human cancers, predominantly among patients with pancreatic cancer, NSCLC, or colorectal cancer (CRC). The company believes RMC-9805 is the first oral and covalent inhibitor of KRASG12D.

The company presented preclinical data on RMC-9805 at the AACR (Free AACR Whitepaper) 2023 Annual Meeting, which demonstrated that inhibiting KRASG12D signaling in cancer cells can sensitize pancreatic ductal adenocarcinoma tumors to immunotherapy.

The company currently expects to announce dosing of the first patient in a monotherapy dose-escalation study of RMC-9805 in mid-2023.
RAS Innovation Engine
Beyond this first wave of RAS(ON) Inhibitors, the company continues expanding its pipeline of investigational RAS(ON) Inhibitor candidates.

RMC-0708 is a potent, oral, selective, first-in-class non-covalent inhibitor of the KRASQ61H(ON) cancer variant. KRASQ61H is found in lung cancer, CRC, pancreatic cancer, and multiple myeloma. RMC-0708 is the company’s first mutant-selective RAS(ON) Inhibitor drug candidate to engage its RAS target non-covalently. The company presented preclinical data on RMC-0708 at the AACR (Free AACR Whitepaper) 2023 Annual Meeting, which demonstrated the compound drove tumor regressions in various preclinical models of human KRASQ61H tumors.

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

The company continues drug discovery efforts in RAS(ON) Inhibitor pipeline expansion programs focused on RAS mutation hotspots including KRASG12R, KRASG12V, KRASG13D, RASQ61X, and other important targets.
RAS Companion Inhibitors

RMC-4630 (SHP2)
RMC-4630 is a clinical-stage, oral inhibitor of SHP2, which contributes to tumor survival and growth in many RAS-addicted cancers. While currently being evaluated in combination with sotorasib, RMC-4630 is also under consideration for combination studies with other RAS inhibitors.

RMC-4630 and KRASG12C Inhibitor Lumakras (sotorasib)

Revolution Medicines continues conducting its global Phase 2 trial RMC-4630-03 (NCT05054725), a multicenter, open-label study of RMC-4630 in combination with sotorasib for patients with NSCLC with a KRASG12C mutation who have failed prior standard therapy and who have not previously been treated with a KRASG12C inhibitor. The company is conducting the trial in collaboration with Amgen, which is supplying sotorasib to trial sites globally. The study is fully enrolled, and Revolution Medicines is on track to provide topline data from this study in the second half of 2023.
RMC-5552 (mTORC1/4EPB1)
RMC-5552 is a first-in-class, bi-steric mTORC1-selective inhibitor designed to suppress phosphorylation and inactivation of 4EBP1 in cancers with hyperactive mTORC1 signaling, including certain RAS-addicted cancers. The company aims to combine RMC-5552 with RAS(ON) Inhibitors in patients with cancers harboring RAS/mTOR pathway co-mutations.

Dose optimization continues in the company’s ongoing multicenter, open-label, Phase 1/1b dose-escalation study evaluating RMC-5552 monotherapy in patients with refractory solid tumors (NCT04774952).

The company currently anticipates disclosing additional evidence of single agent activity for this compound in Q4 2023.
First Quarter 2023 Corporate Highlights

Financing

In March 2023, the company completed an upsized public offering of common stock, raising gross proceeds of $345 million before deducting underwriting discounts, commissions and offering expenses. This included the exercise in full by the underwriters of their option to purchase additional shares of common stock. These funds will be used to strengthen the company’s balance sheet and overall financial position to support the continued development and expansion of its product pipeline.

Addition of New Leaders

The company has made several strategic leadership hires across late-stage clinical development, regulatory and commercial planning, including:

Wei Lin, M.D., chief medical officer, oversees the strategic aspects of clinical development and the organization’s medical affairs function. Wei joins Revolution Medicines from Erasca, where he served as chief medical officer. Prior to his tenure at Erasca, he served as head of development for Nektar Therapeutics, and led a broad registrational program in collaboration with Bristol Myers Squibb to develop IO combination therapy across multiple solid tumor indications. Wei started his industry career at Genentech, where he led the clinical development of the anti-PDL1 antibody TECENTRIQ and its global approval in several lung cancer indications, as well as the early-stage development PI3 kinase inhibitor programs across multiple tumor types. He also served as the clinical development site head for Roche in the Asia Pacific region and led the approval of AVASTIN, TARCEVA, and ZELBORAF in China. Wei obtained his M.D. at Harvard Medical School and completed his medical training at Massachusetts General Hospital and medical oncology fellowship at MD Anderson Cancer Center. He brings deep oncology expertise and a breadth of global development experience to the company’s strong R&D organization, supporting plans to transition its clinical pipeline from early to late-stage clinical development.

Alicia Gardner, senior vice president, commercial, leads the organization’s commercial function. With more than 20 years of commercial experience across biotech and pharmaceutical companies, Alicia most recently served as vice president at Genentech. During her tenure she worked across the company’s oncology/hematology portfolio, where she served as lifecycle leader of cancer immunotherapy with responsibility for the development and commercialization of TECENTRIQ across bladder, renal, and prostate cancer. She also led the marketing team charged with the development of strategy and launch readiness for Genentech’s hematology franchise, including RITUXAN, GAZYVA, and VENCLEXTA across non-Hodgkin’s lymphoma and chronic lymphocytic leukemia.
Nisha Brown, vice president of commercial development, joins the company from Genentech where she held various positions across sales and marketing. Nisha leads commercial launch planning for the company’s programs.
Zane Rogers, vice president of regulatory affairs, joins the company from Atreca, Inc. where he was the head of regulatory and quality. Zane is responsible for regulatory strategy and interactions with regulatory authorities.

Sriram Naganathan, vice president of chemistry, manufacturing, and controls (CMC), joins the company from Nurix Therapeutics where he led the CMC function. Sriram leads CMC efforts at the company, providing strategic and technical guidance for drug substance development and manufacturing operations to enable the company’s growing clinical programs.
First Quarter 2023 Financial Highlights

Cash Position: Cash, cash equivalents and marketable securities were $909.8 million as of March 31, 2023, compared to $644.9 million as of December 31, 2022. The increase was primarily attributable to the company’s public equity offering in March 2023.

Revenue: Total revenue was $7.0 million for the quarter ended March 31, 2023, compared to $7.6 million for the quarter ended March 31, 2022, and consisted of revenue from the company’s collaboration agreement on SHP2 inhibitors with Sanofi.

R&D Expenses: Research and development expenses were $68.9 million for the quarter ended March 31, 2023, compared to $56.5 million for the quarter ended March 31, 2022. The increase was primarily due to an increase in RMC-6236 and RMC-6291 expenses as a result of commencing clinical trials in 2022, an increase in personnel-related expenses related to additional headcount, and an increase in stock-based compensation.

G&A Expenses: General and administrative expenses were $13.2 million for the quarter ended March 31, 2023, compared to $9.0 million for the quarter ended March 31, 2022. The increase was primarily due to an increase in stock-based compensation and an increase in personnel-related expenses related to additional headcount.

Net Loss: Net loss was $68.1 million for the quarter ended March 31, 2023, compared to net loss of $57.6 million for the quarter ended March 31, 2022.

Financial Guidance

Revolution Medicines is updating its financial guidance and now expects full year 2023 GAAP net loss to be between $360 and $400 million, which includes estimated non-cash stock-based compensation expense of $40 million and $50 million. The increase in expected 2023 GAAP net loss is a result of increased investments to support and strengthen clinical advancement of our first wave of RAS(ON) Inhibitors, including expanding clinical supply and strengthening senior leadership across late-stage development, manufacturing, and commercial planning for RMC-6236.

Based on the company’s current operating plan, the company projects current cash, cash equivalents and investments can fund planned operations into 2025.

Webcast
Revolution Medicines will host a webcast this afternoon, May 8, 2023, at 4:30 p.m. Eastern Time (1:30 p.m. Pacific Time). To listen to the live webcast, or access the archived webcast, please visit: View Source Following the live webcast, a replay will be available on the company’s website for at least 14 days.

On May 8, 2023 Recursion (Nasdaq: RXRX), a clinical stage TechBio company leading the space by decoding biology to industrialize drug discovery, reported business updates and financial results for its first quarter ending March 31, 2023 (Press release, Recursion Pharmaceuticals, MAY 8, 2023, View Source [SID1234631175]).

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"Recursion has pioneered the massive, parallel generation of -omics data with machine learning in order to map and navigate biology to discover new medicines faster. The strategic acquisitions of Cyclica and Valence add industry-leading capabilities in digital chemistry, as well as machine-learning and artificial intelligence, which combined with our large-scale automated wet-laboratories and supercomputing capabilities, enables us to deploy what I believe is the most complete, technology-enabled drug discovery solution in the biopharma industry. We look forward to showing the world proof of the compounding benefit of this full-stack approach through the rapid acceleration of our pipeline and partnerships. Amidst a rapidly accelerating global race for technology talent, these acquisitions cement Recursion as the center of gravity for the best and brightest in ML and AI who want to reimagine how drugs are discovered," said Chris Gibson, Ph.D., Co-Founder and CEO of Recursion. "I am so excited to welcome the Cyclica and Valence teams to Recursion, especially at such a dynamic moment in history when machine learning and artificial intelligence are creating so much rapid change across every industry."

Summary of Business Highlights
•Digital Chemistry and Generative AI Acquisitions
◦Cyclica: Cyclica has built an industry-leading digital chemistry software suite which enables mechanism of action deconvolution, generative chemistry and molecular optimization tools. Recursion completed a prospective, blinded evaluation of their software against challenging internal programs, where we gained deep confidence in the power of their tools and reinforced our belief that this team could accelerate Recursion’s work across its pipeline and partnerships by rapidly advancing the discovery of new chemical entities. We believe that Cyclica’s tools will enhance the optimization of our compounds for efficacy while minimizing liabilities through generative machine learning approaches. The company is located in Toronto, where Recursion maintains its biggest hub outside of its headquarters, and the teams at Cyclica will be fully integrated into Recursion.

◦Valence: Valence is a ML/AI-native digital chemistry company which has pioneered the development of novel hybrid graph neural networks and transformers for state-of-the-art chemical property prediction. The small team at Valence has led a massive open-science movement with a network of academic collaborators at the pinnacle of machine learning, chemistry and other fields. Based in Montréal, where Recursion also maintains a ML research team, Valence will work on cutting-edge applied ML research across chemistry and biology. We believe that the technology they have built and will build will enable acceleration of our work at Recursion across many fields, beginning with generative design of new molecules, DMPK predictions and more. Combined with Recursion’s wet-lab data generation capabilities and one of the largest relatable datasets in the industry, the team will also accelerate ongoing internal work to build foundation models, large-language models and other approaches leveraging active learning.

◦Financial Impact of Acquisitions: Recursion has entered into agreements to acquire Cyclica for a purchase price of $40 million and Valence for a purchase price of $47.5 million, in each case subject to customary closing and post-closing purchase price adjustments. The purchase price in the acquisitions will be payable in the form of shares of Recursion Class A common stock, shares of a subsidiary of Recursion exchangeable for shares of Recursion’s Class A common stock and the assumption of certain outstanding Valence and Cyclica options. In certain circumstances, Recursion may pay cash consideration to Valence and Cyclica shareholders in lieu of such exchangeable shares or Recursion Class A common stock. Recursion expects no material change to its cash runway as a result of these acquisitions. Recursion expects both acquisitions to be completed in the second quarter of 2023, subject to applicable closing conditions.

•Internal Pipeline

◦Cerebral Cavernous Malformation (CCM) (REC-994): Our Phase 2 SYCAMORE clinical trial is a double-blind, placebo-controlled safety, tolerability and exploratory efficacy study of this drug candidate in 60 participants with CCM. We have enrolled the majority of participants associated with this study, and most participants who have finished their first year of treatment have now enrolled in the long-term extension study. We expect to share top-line data in H2 2024.
◦Neurofibromatosis Type 2 (NF2) (REC-2282): Our Phase 2/3 POPLAR clinical trial is a parallel group, two stage, randomized, multicenter study of this drug candidate in approximately 90 participants with progressive NF2-mutated
meningiomas. Enrollment is ongoing and we expect to share a Phase 2 interim safety analysis in 2024.
◦Familial Adenomatous Polyposis (FAP) (REC-4881): Our Phase 2 TUPELO clinical trial is a multicenter, randomized, double-blind, placebo-controlled two-part clinical trial to evaluate efficacy, safety, and pharmacokinetics of this drug candidate in patients with FAP. We continue to advance this study.

◦AXIN1 or APC Mutant Cancers (REC-4881): REC-4881 is being studied for the potential treatment of AXIN1 or APC mutant cancers with an initial focus on solid tumors harboring these mutations. We are developing a Phase 2 open-label study for REC-4881 in participants with unresectable, locally advanced or metastatic cancer with AXIN1 or APC mutations. We expect to initiate a Phase 2 biomarker enriched study across select AXIN1 or APC mutant solid tumors in early 2024.
◦Clostridioides difficile Colitis (REC-3964): Our Phase 1 clinical trial is a first-in-human protocol evaluating single and multiple doses of REC-3964 in healthy volunteers and will assess the safety, tolerability and pharmacokinetic profile of REC-3964. We have enrolled the majority of participants associated with this study, and REC-3964 has been well tolerated to date. We expect to share safety and PK data in H2 2023.
◦RBM39 HR-Proficient Ovarian Cancer: In January 2023, we disclosed that RBM39 (previously identified as Target Gamma) is the novel CDK12-adjacent target identified by the Recursion OS. We believe that we can modulate this target to produce a potentially therapeutic effect in HR-proficient ovarian cancer. We have advanced this program to the preclinical stage and have initiated IND-enabling studies.
•Transformational Collaborations
We continue to advance efforts to discover potential new therapeutics with our strategic partners in the areas of neuroscience and a single indication in gastrointestinal oncology (Roche-Genentech) as well as fibrotic disease (Bayer). In the near-term, there is the potential for option exercises associated with partnership programs, option exercises associated with map building initiatives or data sharing and additional partnerships in large, intractable areas of biology or technological innovation.
•Recursion OS
◦Industrialized Program Generation: This end-to-end process validates map-based insights without human intervention. Following the proposal of disease model starting points, Industrialized Program Generation carries out the programmatic selection of compound hits, compound ordering coordination, and validation through phenomic and transcriptomic profiling. Given the large number of proto-programs that are expected from this process, we look forward to leveraging the digital chemistry technology and expertise of the Cyclica and Valence teams to design and optimize chemical structures for novel biological targets.

Additional Corporate Updates

•ESG Reporting: In March 2023, Recursion released its second annual ESG report. Materials from this report can be found at www.Recursion.com/esg.
•Annual Shareholder Meeting: The Recursion Annual Shareholder Meeting will be held on June 16, 2023 at 12:00 pm Mountain Time. In preparation for this meeting, Recursion released its annual Proxy Statement in April 2023.

First Quarter 2023 Financial Results
•Cash Position: Cash and cash equivalents were $473.1 million as of March 31, 2023.
•Revenue: Total revenue was $12.1 million for the first quarter of 2023, compared to $5.3 million for the first quarter of 2022. The increase was due to progress made in our Roche-Genentech collaboration.
•Research and Development Expenses: Research and development expenses were $46.7 million for the first quarter of 2023, compared to $32.4 million for the first quarter of 2022. The increase in research and development expenses was due to increased platform costs as we have expanded and upgraded our capabilities.
•General and Administrative Expenses: General and administrative expenses were $22.9 million for the first quarter of 2023, compared to $21.1 million for the first quarter of 2022. The increase in general and administrative expenses was due to an increase in salaries and wages of $1.2 million and increases in other administrative costs associated with growth in the size of the Company’s operations.
•Net Loss: Net loss was $65.3 million for the first quarter of 2023, compared to a net loss of $56.0 million for the first quarter of 2022.

On May 8, 2023 Primmune Therapeutics, a biotech company harnessing the power of the innate immune system to treat solid tumors in the advanced cancer setting and to clear human papillomavirus and related pre-cancerous cervical lesions, reported that Primmune’s Senior Vice President & Chief Scientific Officer James Appleman, Ph.D., will present at the 4th STING & TLR-Targeting Therapies Summit being held in Boston, Massachusetts from May 9-11, 2023 (Press release, Primmune Therapeutics, MAY 8, 2023, View Source [SID1234631174]).

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

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The oral presentation will cover the recent clinical progress of PRTX007, a systemically active, orally administered prodrug of a novel, small molecule toll-like receptor 7 (TLR7)-specific agonist and will evaluate how the unique pharmacology elicited by PRTX007 distinguishes Primmune’s lead candidate from other TLR7 agonists in human cellular models, in non-human primates, and in the clinical setting. The presentation at the Summit will also review how PRX034, the TLR7 agonist systemically delivered by PRTX007, has been shown to induce engagement of the innate and adaptive immune responses while avoiding systemic inflammation in healthy volunteers, and why PRTX007’s favorable profile is expected to correlate with efficacy in cancer therapy.

Presentation details:

Title: PRTX007, a Novel Orally Administered TLR7 Agonist Prodrug from Primmune Therapeutics for the Treatment of Cancer
Presenter: James Appleman, Ph.D.
Date and Time: Wednesday, May 10 at 10 a.m. ET
Location: Hilton Boston Back Bay

More information on the conference can be found here.

About PRTX007
PRTX007, Primmune’s lead clinical development candidate, is designed to provide well-tolerated, controlled, long-term stimulation of the innate immune response while also potentiating long-term effective innate and adaptive immune responses. PRTX007 administration uniquely activates plasmacytoid dendritic cells (pDCs), leading to a systemic immune poly-IFN response without stimulating production of NF-κB-driven proinflammatory factors like IL-6, TNFα or IL-1β. Activated pDCs directly deliver interferons to target cells by paracrine transfer. Conceptually, this is equivalent to administering a therapeutically effective cocktail of all Type I/III IFNs while avoiding the associated side effects and adverse events. Furthermore, PRTX007 administration leads to systemic activation of anti-tumor effector CD8+ T cells and NK cells. PRTX007 is being rapidly advanced towards clinical trials for solid tumors in the advanced cancer setting and for clearing human papillomavirus-transformed pre-cancerous cervical lesions.

On May 8, 2023 Prelude Therapeutics Incorporated (Nasdaq: PRLD), a clinical-stage precision oncology company, reported financial results for the first quarter ended March 31, 2023, and provided an update on recent clinical and development pipeline progress (Press release, Prelude Therapeutics, MAY 8, 2023, View Source [SID1234631173]).

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

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"Our recent presentations at the 2023 AACR (Free AACR Whitepaper) Annual Meeting highlight the meaningful progress we made across our clinical and preclinical pipeline programs. In addition to our clinical presentations on PRT2527 (CDK9 inhibitor) and PRT1419 (MCL-1 Inhibitor) that demonstrated differentiated and potential best-in-class PK/PD profiles of these molecules, our preclinical research demonstrated the promise of our pipeline in addressing unmet patient needs in cancer through combination approaches. Patient enrollment in the phase 1 dose escalation of PRT3789 (first-in-class SMARCA2 selective degrader) is now underway. Our teams are focused on advancing our pipeline to key milestones and we look forward to reporting further updates in the coming months," said Kris Vaddi, Ph.D., Chief Executive Officer of Prelude.

Recent Highlights

2023 AACR (Free AACR Whitepaper) Annual Meeting: Prelude participated in the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, presenting two clinical and six preclinical poster presentations. Initial safety, pharmacokinetic and pharmacodynamic profiles in solid tumors for both PRT2527 and PRT1419 were presented. Preclinical data for both the Company’s next generation CDK4/6 inhibitor, PRT3645, and the SMARCA2 degrader, PRT3789, in combination with other targeted therapies, demonstrated the combinability of these compounds with standard of care medicines and inform potential clinical development.

Program Updates and Upcoming Milestones

PRT2527- CDK9 Inhibitor Program
PRT2527, Prelude’s potentially best in class CDK9 inhibitor, is completing a solid tumor dose escalation study. In adults with advanced solid tumors, PRT2527 was generally well-tolerated with manageable neutropenia and absence of significant gastrointestinal events or hepatotoxicity. The short half-life of PRT2527 enables acute CDK9 inhibition over a defined period making it potentially suitable for weekly administration without inducing significant toxicity. The observed dose-dependent downregulation of CDK9 transcriptional targets – MYC and MCL-1 mRNA expression in PBMCs isolated from patients treated with PRT2527 –was consistent with the degree of target engagement required for preclinical efficacy. The 15 m/mg2 QW dose of PRT2527 was selected for further evaluation in dose-confirmation cohort.

The overall safety profile observed in this study supports further development of PRT2527 in combination with other targeted therapies, including in hematologic malignancies. The Company is on track to establish a RP2D in hematological malignancies in 2H 2023.

PRT1419- MCL1 Inhibitor Program
PRT1419 demonstrated an acceptable safety and tolerability profile in patients with advanced and metastatic solid tumors, with the most common TRAEs of nausea, vomiting, and diarrhea. Neutropenia was deemed to be dose related. No cardiac toxicity was observed. Pharmacokinetics/pharmacodynamics and safety data in the 80 mg/m2 QW PRT1419 dose cohort support further evaluation of this dose in future studies. Induction of activated-BAX and cleaved caspase-3 was observed at 80 and 120 mg/m2 QW PRT1419, suggesting successful MCL-1 inhibition. No tumor reductions met response criteria. Further investigation of PRT1419 in patients with hematologic malignancy is ongoing. The Company is on track to determine the RP2D in hematological RP2D and will provide a clinical update at year end.

PRT3645-Next Generation CDK4/6 Inhibitor Program
Prelude showed that PRT3645 is highly efficacious when combined with KRAS/MEK inhibitors, and with a brain penetrant HER2 receptor kinase inhibitor in in vivo preclinical models.

Additionally, oral administration of PRT3645 induces tumor regression in palbociclib-resistant preclinical models. Dose escalation phase of PRT3645 is progressing per plan and the Company expects to provide an update by year end.

PRT3789 SMARCA2 Targeted Protein Degrader Program
Phase 1 dose escalation of PRT3789 (first-in-class selective SMARCA2 degrader) is ongoing. The Company recently presented preclinical data, showing that SMARCA2 selective degraders demonstrate anti-proliferation activity and promote cell differentiation in a wide range of indications demonstrating activity as monotherapy, as well as in combination with KRAS G12C inhibitors, chemotherapy and other targeted agents. Consistent with the Company’s plans to nominate an orally bioavailable candidate in early 2024, preclinical data at AACR (Free AACR Whitepaper) showed that oral administration of multiple internally developed compounds results in significant tumor growth inhibition of SMARCA4-deficient lung cancer xenografts at well-tolerated doses.

First Quarter 2023 Financial Results

Cash, Cash Equivalents and Marketable Securities: Cash, cash equivalents, and marketable securities as of March 31, 2023, were $172.3 million. Prelude anticipates that its existing cash, cash equivalents and marketable securities will fund the Company’s operations into the fourth quarter of 2024.

Research and Development (R&D) Expenses: For the first quarter of 2023, R&D expense decreased to $21.8 million from $22.8 million for the prior year period. Research and development expenses decreased primarily due to the timing of our clinical research programs. We expect our R&D expenses to vary from quarter to quarter, primarily due to the timing of our clinical development activities.

General and Administrative (G&A) Expenses: For the first quarter of 2023, G&A expenses were relatively unchanged as compared to the three months ended March 31, 2022.

Net Loss: For the three months ended March 31, 2023, net loss was $27.7 million, or $0.58 per share compared to $29.5 million, or $0.63 per share, for the prior year period. Included in the net loss for the quarter ended March 31, 2023, was $6.3 million of non-cash expense related to the impact of expensing share-based payments, including employee stock options, as compared to $6.8 million for the same period in 2022.