On May 10, 2021 IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a synthetic lethality focused precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported financial results for the first quarter ended March 31, 2021 (Press release, Ideaya Biosciences, MAY 10, 2021, View Source [SID1234579589]).

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"We are excited to advance IDE397, a potential best-in-class MAT2A inhibitor, in the Phase 1 dose escalation for evaluation in patients with MTAP deletion tumors, including in non-small cell lung cancer (NSCLC). We are also continuing to invest in our preclinical synthetic lethality programs, including our PARG and Pol Theta programs for patients with HRD tumors, where we are targeting a development candidate for both programs in 2021," said Yujiro S. Hata, Chief Executive Officer and President of IDEAYA Biosciences.

"We are excited by the preliminary darovasertib monotherapy overall survival data in MUM and look forward to receiving FDA regulatory guidance based on the data in the second half of 2021. We are also executing on our darovasertib clinical combination strategy and are encouraged by the early partial responses observed in the combination arms, including now in the crizotinib combination. Importantly, the 54% tumor reduction by RECIST 1.1 observed in a patient treated with the darovasertib and crizotinib combination is the deepest partial response we have seen to date in the darovasertib Phase 1/2 clinical trial," said Matthew Maurer, M.D., Vice President, Head of Clinical Oncology and Medical Affairs, IDEAYA Biosciences.

Program Updates
Key highlights for IDEAYA’s pipeline programs include:
IDE397 (MAT2A)
IDEAYA is evaluating IDE397, a potent and selective small molecule inhibitor targeting methionine adenosyltransferase 2a (MAT2A), in patients having solid tumors with methylthioadenosine phosphorylase (MTAP) deletion, a patient population estimated to represent approximately 15% of solid tumors. IDEAYA is leading early clinical development of IDE397. Subject to exercise of its option, GlaxoSmithKline (GSK) will lead later stage global clinical development. Highlights:

Initiated a Phase 1 clinical trial designated as IDE397-001 (ClinicalTrials.gov Identifier: NCT04794699) to evaluate IDE397 under an investigational new drug application
Completed enrollment into an initial dose escalation cohort of the Phase 1 clinical trial
Clinical development plans for IDE397 include a dose escalation portion of the Phase 1 clinical trial in which IDEAYA is enrolling patients having solid tumors with MTAP gene deletion. Patients are being identified by next generation sequencing (NGS) or by MTAP immunohistochemistry (IHC) assay with confirmatory NGS
Subject to satisfactory completion of the dose escalation portion of the Phase 1 clinical trial, IDEAYA plans to enroll MTAP deletion patients into expansion arms in NSCLC and potentially in other solid tumor indications such as esophageal, gastric, bladder, head and neck, or pancreatic cancers
Planning to obtain patient biopsies from the dose escalation and expansion portions of the clinical trial for translational research, including evaluation of certain pharmacodynamic, or PD, biomarkers, such as peripheral S-adenosyl methionine (SAM), tumor SAM and tumor symmetric dimethylarginine (SDMA)
Program objective is to obtain preliminary clinical PD data from the dose-escalation portion of the IDE397 monotherapy Phase 1 clinical trial in the second half of 2021
Demonstrated preclinical efficacy of monotherapy IDE397 in a study of over forty solid tumor patient derived xenograft (PDX) models with homozygous MTAP deletions across a range of solid tumor types, including NSCLC, esophageal, gastric, bladder, head and neck, and pancreatic cancers; study data was reported at AACR (Free AACR Whitepaper) 2021 and showed:
tumor regressions, with >100% tumor growth inhibition, or TGI, in multiple PDX models across multiple solid tumor types, including in NSCLC as well as in bladder and gastric cancer models
>75% TGI in approximately 50% of models and across major solid tumor types
>60% TGI in approximately 75% of models and across major solid tumor types
dose-dependent modulation of PD biomarkers, including SDMA and SAM
Observed single-agent IDE397 preclinical activity in NSCLC PDX models, demonstrating >60% TGI in 11 independent PDX models out of 13 models evaluated in the MTAP-deletion PDX panel study, including in 7 of 9 NSCLC adenocarcinoma PDX models, and in 4 of 4 NSCLC squamous carcinoma PDX models evaluated, and demonstrating tumor regressions in 2 of 4 NSCLC squamous PDX models, including one complete response
Showed correlation of in vivo efficacy with PD modulation of tumor SDMA and tumor SAM in a study evaluating IDE397 in an MTAP-deletion NSCLC CDX model
Reported preclinical analyses of genomic and metabolic effects of pharmacological inhibition of MAT2A in an isogenic cell pair and of proliferation effects in a panel of MTAP wild type and MTAP-deleted cell lines at AACR (Free AACR Whitepaper) 2021
Observed in vivo efficacy of IDE397 in combination with a taxane, showing enhanced TGI in a pancreatic cancer PDX model, and separately in combination with a PRMT inhibitor, showing enhanced TGI in an HCT116 MTAP-null CDX model
PARG
IDEAYA is advancing preclinical research for an inhibitor of poly (ADP-ribose) glycohydrolase (PARG) in patients having tumors with a defined biomarker based on genetic mutations and/or molecular signature. PARG is a novel target in the same clinically validated biological pathway as poly (ADP-ribose) polymerase (PARP). IDEAYA owns or controls all commercial rights in its PARG program. Highlights:

Identified a novel and proprietary HRD biomarker to guide patient selection, with validation in vitro and in vivo in CDX models across multiple solid tumor indications
Demonstrated PARGi dose-dependent in vivo efficacy as monotherapy with tumor regression or stasis in ovarian, gastric and breast cancer CDX models
Observed in vivo efficacy with enhanced TGI or tumor regressions relative to niraparib, a PARPi, in multiple CDX models, including in a niraparib-resistant CDX model
Showed tumor regressions in multiple breast cancer PDX models with defined genetic and subtyping profiles
Reported preclinical data at AACR (Free AACR Whitepaper) 2021, including pharmacological inhibition of PARG in a panel of homologous recombination deficient cell lines and in CDX and PDX models
Subject to further preclinical studies, IDEAYA is targeting to identify a PARG inhibitor development candidate in 2021
Pol Theta
IDEAYA’s DNA Polymerase Theta, (Pol Theta) program targets tumors with BRCA or other homologous recombination deficiency, or HRD, mutations. IDEAYA and GSK are collaborating on ongoing preclinical research, including small molecules and protein degraders, and GSK will lead clinical development for the Pol Theta program. Highlights:

Demonstrated in vivo efficacy with tumor regression in BRCA2 -/- xenograft model with IDEAYA Pol Theta inhibitor in combination with niraparib, a GSK PARP inhibitor; and
Subject to further preclinical studies, IDEAYA is targeting selection of a Pol Theta inhibitor development candidate in 2021
Werner Helicase
IDEAYA is advancing preclinical research for an inhibitor targeting Werner Helicase for tumors with high microsatellite instability (MSI). IDEAYA and GSK are collaborating on ongoing preclinical research, and GSK will lead clinical development for the Werner Helicase program. Highlights:

observed dose-dependent cellular viability effect and dose-dependent cellular PD response in multiple endogenous MSI high cell lines
Demonstrated in vivo efficacy and PD response in relevant MSI high models
Other Synthetic Lethality Pipeline Programs
IDEAYA is advancing additional preclinical research programs to identify small molecule inhibitors for an MTAP-synthetic lethality target, as well as for multiple distinct DNA Damage Targets for patients with solid tumors characterized by a proprietary biomarker or a gene signature.

Darovasertib (IDE196)
IDEAYA continues to execute on its clinical trial strategy to evaluate darovasertib (IDE196), a potent and selective PKC inhibitor.

IDEAYA is evaluating darovasertib in metastatic uveal melanoma (MUM) as monotherapy and in combination therapies, including combinations of darovasertib / binimetinib and independently, darovasertib / crizotinib. The company is continuing to enroll MUM patients into each of these combination arms of the Phase 1/2 clinical trial, and it targeting to provide a clinical data update for the darovasertib combination(s) in the second half of 2021. Based on preliminary monotherapy clinical data in MUM and its mechanism of action, we anticipate darovasertib clinical activity independent of Human Leukocyte Antigen (HLA) status in GNAQ/11-mutation cancers.

The company is also evaluating darovasertib as monotherapy outside of MUM, with a focus in GNAQ/11-mutation skin melanoma.

Darovasertib Monotherapy
IDEAYA has completed enrollment into its ongoing Phase 1/2 clinical trial evaluating darovasertib as monotherapy in MUM patients. IDEAYA is targeting to receive FDA guidance in H2 2021 on potential regulatory path, based on the preliminary darovasertib monotherapy overall survival data in MUM. The company is continuing enrollment into its ongoing basket trial evaluating darovasertib as monotherapy in patients having non-MUM tumors harboring GNAQ or GNA11 activating mutations. The company’s development strategy in the monotherapy non-MUM GNAQ/11 arm of the clinical trial is focused on skin melanoma. Highlights:

Reported interim clinical data from Phase 1/2 clinical trial arm evaluating monotherapy darovasertib in predominantly second and third line (2L/3L) and heavily pre-treated out to seventh or eighth line (7L/8L) MUM patients. As of data and analyses cutoff on April 13, 2021 based on preliminary data from an unlocked database:
Enrolled an aggregate of 81 darovasertib monotherapy BID MUM patients across the IDEAYA and Novartis Phase 1/2 clinical trials, with 81 patients evaluable for safety and 75 patients evaluable for efficacy pursuant to RECIST 1.1 guidelines
Observed 57% 1-year overall survival (OS) with 95% confidence interval (44%, 69%), in predominantly 2L/3L and heavily pretreated to 7L/8L patients
Observed median OS of 13.2 months with 95% confidence interval (10.7 months, not reached), in predominantly 2L/3L and heavily pretreated to 7L/8L patients
Historical 37% 1-year OS and median OS of ~7 months have been reported in similar 2L/3L+ MUM patient population (Rantala 2019)
Observed tumor reduction in 61% (n=46) of 75 evaluable MUM patients pursuant to RECIST 1.1 guidelines, including 15 patients (20%) with >30% target lesion reduction, and one confirmed complete response
Reported preliminary clinical data from Phase 1/2 clinical basket trial arm evaluating monotherapy darovasertib in skin melanoma patients. As of data and analyses cutoff of April 13, 2021 based on preliminary data from an unlocked database:
Enrolled 7 darovasertib monotherapy BID skin melanoma patients in the IDEAYA Phase 1/2 clinical trial, with 7 patients evaluable for safety and 5 patients evaluable for efficacy pursuant to RECIST 1.1 guidelines
Observed tumor reduction in 80% (n=4) of 5 evaluable skin melanoma patients pursuant to RECIST1.1 guidelines, including one confirmed PR
An aggregate of 88 patients were evaluable for safety across Phase 1/2 arms evaluating darovasertib in MUM and skin melanoma patients. As of the April 13, 2021 data and analyses cutoff, and based on preliminary data from an unlocked database, the overall safety profile of darovasertib monotherapy is consistent with prior experience and includes primarily common low grade but manageable GI and skin toxicities
Preliminary clinical data from darovsertib monotherapy arm shows that darovasertib activity is independent of HLA status
Darovasertib / Binimetinib Combination Therapy
IDEAYA is continuing patient enrollment into the darovasertib / binimetinib combination arm of the Phase 1/2 clinical trial under the clinical trial collaboration and supply agreement with Pfizer. Highlights:

Initiated dose expansion evaluating the darovasertib / binimetinib combination in MUM based on early clinical activity
Amended the clinical trial collaboration and supply agreement with Pfizer to support target enrollment of approximately 40 patients in the darovasertib and binimetinib clinical combination arm
Reported preliminary clinical data from Phase 1/2 clinical trial arm evaluating the darovasertib / binimetinib combination in MUM patients, predominantly as second line, third line (2L / 3L) or later lines of treatment. As of data and analyses cutoff of April 13, 2021 based on preliminary data from an unlocked database:
24 MUM patients have enrolled in the darovasertib and binimetinib combination study and 14 of these patients were evaluable, including eight patients dosed in the Phase 1/2 dose expansion cohort of the combination study
Observed 22% (n=2) partial responses (PR), including one confirmed PR and on unconfirmed PR awaiting a confirmatory scan, of nine evaluable MUM patients with at least two post-baseline scans pursuant to RECIST 1.1 guidelines
Observed tumor reduction in 79% (n=11) of 14 evaluable MUM patients with at least one post-baseline scan pursuant to RECIST1.1 guidelines
Drug-related adverse events observed in the darovasertib and binimetinib combination arm in MUM, as of April 13, 2021 data and analyses cutoff based on preliminary data from an unlocked database, primarily include: serious adverse events of liver toxicity, nausea and vomiting, and syncope; and adverse events that occurred in greater than 10% of patients of nausea, vomiting, diarrhea, rash, edema, aminotransaminase, or AST increase, alanine aminotransferase, or ALT, increase and creatine phosphokinase increase
Darovasertib / Crizotinib Combination Therapy
IDEAYA is continuing patient enrollment into the darovasertib / crizotinib combination arm of the Phase 1/2 clinical trial under the clinical trial collaboration and supply agreement with Pfizer. Highlights:

6 MUM patients have enrolled in the darovasertib and crizotinib combination study and 2 of these patients were evaluable for response with one post-baseline scan
Observed early clinical efficacy of the darovasertib and crizotinib combination in MUM. As of data and analyses cutoff on May 5, 2021 based on preliminary data from an unlocked database, these data showed:
tumor reduction in 2 of 2 evaluable patients in a first cohort
one unconfirmed partial response in a 3rd-line patient, with a 54% tumor reduction, which is the deepest response, as reflected by the largest percentage reduction in tumor size, reported in the darovasertib clinical trial to date; this patient is awaiting a confirmatory scan
Drug-related adverse events observed in the darovasertib and crizotinib combination arm in MUM as of May 5, 2021, based on preliminary data from an unlocked database, primarily include: serious adverse events of syncope and hypotension, each of which resolved with patients continuing dosing; and adverse events that occurred in at least two of the six treated patients of nausea, diarrhea, vomiting, edema, decreased appetite, and syncope.
Initiated dose expansion for a cohort of the Phase 1/2 darovasertib / crizotinib combination arm, with additional dose exploration ongoing
Observed preclinical synergies between darovasertib and crizotinib in relevant cellular models under conditions simulating a tumor microenvironment in the liver, the site of approximately 90% of uveal melanoma metastases, as reported at AACR (Free AACR Whitepaper) 2021
Correlated cMET expression and activation to observed clinical response based on a retrospective analysis of human clinical biopsies from the Novartis darovasertib Phase 1 clinical trial, supporting cMET expression / activation as potential combination agent
General
IDEAYA continues to monitor Covid-19 and its potential impact on clinical trials and timing of clinical data results. Initiation of clinical trial sites, patient enrollment and ongoing monitoring of enrolled patients, including obtaining patient computed tomography (CT) scans, may be impacted for IDEAYA clinical trials evaluating IDE397 and darovasertib; the specific impacts are currently uncertain.

Corporate Updates
IDEAYA’s net losses were $9.0 million and $5.1 million for the three months ended March 31, 2021 and December 31, 2020, respectively. As of March 31, 2021, the company had an accumulated deficit of $136.0 million.

As of March 31, 2021, IDEAYA had cash, cash equivalents and marketable securities of $310.4 million. IDEAYA supplemented its first-quarter-end cash, cash equivalents and marketable securities with an additional $14.6 million in aggregate gross proceeds received subsequent to quarter end from the sale and issuance of common stock at a weighted average sale price of $22.99 per share under an at-the-market offering pursuant to the January 2021 Sales Agreement with Jefferies as sales agent.

IDEAYA believes that its cash, cash equivalents and marketable securities will be sufficient to fund our planned operations into 2024. These funds will support the company’s efforts through potential achievement of multiple preclinical and clinical milestones across multiple programs.

Our updated corporate presentation is available on our website, at our Investor Relations page: View Source

Financial Results
As of March 31, 2021, IDEAYA had cash, cash equivalents and short-term marketable securities totaling $310.4 million. This compared to cash, cash equivalents and short-term and long-term marketable securities of $283.6 million at December 31, 2020. The increase was primarily due to $41.8 million in net proceeds received through March 31, 2021 from issuance of common stock under at-the-market offerings pursuant to the August 2020 Sales Agreement and January 2021 Sales Agreement with Jefferies as sales agent offset by cash used in operations and purchases of property and equipment.

Collaboration revenue for the three months ended March 31, 2021 totaled $7.2 million compared to $10.6M for the three months ended December 31, 2020. Collaboration revenue was recognized for the performance obligations satisfied through March 31, 2021 under the GSK Collaboration Agreement.

Research and development (R&D) expenses for the three months ended March 31, 2021 totaled $11.6 million compared to $12.1 million for the three months ended December 31, 2020. The decrease was primarily due to a decrease in external clinical development expenses for IDE397 and darovasertib and a decrease in fees to CROs, CMOs and external consultants related to our lead product candidates, offset by an increase in R&D headcount costs.

General and administrative (G&A) expenses for the three months ended March 31, 2021 totaled $4.8 million compared to $3.8 million for the three months ended December 31, 2020. The increase was primarily due to an increase in G&A headcount costs, an increase in legal patent expense, and an increase in costs related to the filing of our shelf registration statement on Form S-3 during the quarter.

The net loss for the three months ended March 31, 2021 was $9.0 million compared to $5.1 million for the three months ended December 31, 2020. Total stock compensation expense for the three months ended March 31, 2021 was $1.9 million compared to $1.0 million for the three months ended December 31, 2020.

On May 10, 2021 Novo Nordisk A/S reported that entered into an agreement to purchase 5,610,000 B shares of DKK 0.20 to a value of DKK 2,586 million from Novo Holdings A/S (Press release, Novo Nordisk, MAY 10, 2021, View Source [SID1234579588]). This transaction is part of Novo Nordisk A/S’ 2021 share repurchase programme of up to a total of DKK 18 billion to be executed during a 12-month period beginning 3 February 2021. The transaction price is DKK 461.04 per share and has been calculated as the three-day volume weighted average market price from 5 May 2021 to 7 May 2021 in the open window following the announcement of Novo Nordisk A/S’ quarterly financial results.

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Prior to the sale of B shares, Novo Holdings A/S’ ownership of Novo Nordisk A/S was 28.5% of the share capital and 76.9% of the votes. Following the transaction, Novo Holdings A/S owns 537,436,000 A shares of DKK 0.20 and 116,129,000 B shares of DKK 0.20, corresponding to 28.3% of the capital and 76.8% of the votes in Novo Nordisk A/S.

The transaction is in line with the announcement on 5 May 2021 that Novo Holdings A/S intends to maintain its ownership of Novo Nordisk A/S’ share capital around 28%.

In addition, transactions related to Novo Nordisk’s incentive programmes have resulted in a net transfer from Novo Nordisk of 9,954 B shares in the period from 5 May 2021 to 7 May 2021.

With the transactions stated above, Novo Nordisk A/S owns a total of 11,257,435 B shares of DKK 0.20, corresponding to 0.5% of the share capital, as treasury shares. The total amount of A and B shares in the company is 2,310,000,000 of DKK 0.20 including treasury shares.

On May 10, 2021 Hamlet Pharma reported the successful outcome of the dose-escalation study, which is an extension of the Phase I/II trial. Patients with bladder cancer were treated with increasing doses of Alpha1H, following a dose-escalation protocol (Press release, HAMLET Pharma, MAY 10, 2021, View Source;utm_medium=rss&utm_campaign=marked-increase-in-tumor-response-with-higher-doses-of-alpha1h [SID1234579587]). The initial data analysis has revealed a dramatic increase in the tumor response to Alpha1H, measured both as shedding of tumor fragments into the urine and as changes in remaining tumor tissue.
Hamlet Pharma has previously reported the successful completion of the Phase I/II bladder cancer study using a 1.7 mM dose of Alpha1H. We have now performed a dose-escalation study, using 8.5 or 17 mM, i.e. five or ten times higher doses in patients with superficial bladder cancer.

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Alpha1H triggered massive shedding of tumor cells and tumor fragments into patient urine. A dose-dependent increase was demonstrated, resulting in significantly higher shedding than in the first study (P<0.0001). As shown earlier, significant cell shedding did not occur in the placebo group, supporting a treatment effect.

Major effects on tumor tissue were detected by histopathology of tumor biopsies, obtained at surgery after the end of treatment. Tumor fragmentation and shedding of tumor fragments was visible and the remaining tumor showed a loss of viability, with large areas of cells undergoing apoptosis or necrosis.

Apoptosis is a beneficial, non-toxic form of cell death, and a desirable outcome to limit the side effects of cancer therapy. In addition to the apoptotic changes in the tumors, a pronounced apoptotic response was detected in cells and tumor fragments shed by the treated patients, confirming that Alpha1H accelerates cell death in the tumor.

Furthermore, the tumor fragments in urine were shown to contain large amounts of Alpha1H, confirming the efficiency with which the higher doses of Alpha1H reach tumor tissue. The results suggest that uptake of Alpha1H by the tumor triggers apotosis, tumor fragmentation and release of the affected tumor fragments by shedding into the urine.

"The dose-dependent increase in tumor response is dramatic and provides further motivation to develop Alpha1H for therapeutic use in bladder cancer," says Catharina Svanborg, founder and chairman of the board of Hamlet Pharma Ltd.

"The results support our strategy to develop Alpha1H for Phase III trials" says Mats Persson, CEO of Hamlet Pharma Ltd.

On May 10, 2021 Pliant Therapeutics, Inc. (Nasdaq: PLRX) ("the Company"), a clinical stage biotechnology company focused on discovering and developing novel therapeutics for the treatment of fibrosis, reported a corporate update and reported first quarter 2021 financial results (Press release, Pliant Therapeutics, MAY 10, 2021, View Source [SID1234579585]).

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"During the first quarter, we continued the strong momentum of advancing our broad and novel clinical and development-stage portfolio," said Bernard Coulie, M.D., Ph.D., President and Chief Executive Officer of Pliant Therapeutics. "With this progress and a financial runway taking us into 2023, we are well positioned to advance toward our objective of bringing potentially transformative treatments to patients in need."

First Quarter and Recent Highlights

PLN-74809 Phase 2a positron emission tomography (PET) imaging trial preliminary data expected in the first half 2021. This open-label, dose ranging trial is evaluating target receptor occupancy levels of PLN-74809 in the lungs of IPF patients across multiple single-dose cohorts utilizing a PET tracer of the integrin αvβ6. The goal of the trial is to confirm the ability of PLN-74809, a dual selective inhibitor of αvβ6/αvβ1, to penetrate highly fibrotic areas of the lung where αvβ6 expression is highest and bind to its target receptor. Additionally, the trial will establish a pharmacokinetic/ pharmacodynamic (PK/PD) relationship between PLN-74809 plasma exposure and αvβ6 receptor occupancy, allowing us to build a PK/PD model that will inform dose selection in later stage trials.

PLN-74809 Phase 2a INTEGRIS trial in idiopathic pulmonary fibrosis (IPF) continued to build momentum, currently on track to complete enrollment by the end of 2021. The primary endpoints of this 12-week randomized, dose-ranging, double-blind, placebo-controlled trial are the evaluation of PLN-74809’s safety, tolerability, and pharmacokinetics in IPF patients. The Company will also evaluate exploratory efficacy endpoints including Quantitative Lung Fibrosis, or QLF, imaging as well as pulmonary function tests.

PLN-74809 Phase 2a INTEGRIS trial in primary sclerosing cholangitis (PSC) continued to advance, currently on track to complete enrollment in the first half 2022. The primary endpoints of this 12-week randomized, dose-ranging, double-blind, placebo-controlled trial are the evaluation of PLN-74809’s safety, tolerability, and pharmacokinetics in PSC patients. The Company will also evaluate exploratory efficacy endpoints including fibrosis biomarkers such as Pro-C3 and ELF, changes in ALP, and liver imaging.

Successful completion of PLN-1474 Phase 1 trial and transfer of PLN-1474 to Novartis. The Phase 1 trial of PLN-1474 was a safety, tolerability, and pharmacokinetics dose-escalating first-in-human trial that enrolled 84 healthy volunteers. PLN-1474 was rapidly absorbed and well tolerated with no dose-or treatment-limiting toxicities or severe/ serious adverse events observed. In preclinical studies, PLN-1474 was observed to selectively block the αvβ1 integrin-mediated activation of TGF-β, reducing liver fibrosis in animal models. Following the successful completion of this study, PLN-1474 has been transferred to Novartis.
COVID-19 Preparedness

The Company continues to develop and maintain policies and procedures to enable us to operate safely and productively during the COVID-19 pandemic. The Company has experienced delays in clinical trial operations which have impacted and may further impact the expected timing of data readouts. The Company continues to work closely with clinical sites to continue site initiation and operation activities in compliance with study protocols while observing government and institutional guidelines.

First Quarter 2021 Financial Results

Research and development expenses were $18.5 million, as compared to $13.9 million for the prior-year quarter. The increase was due primarily to employee related expenses and higher costs related to the advancement of several programs and ongoing Phase 1/2 clinical trials.
General and administrative expenses were $6.6 million, as compared to $4.0 million for the prior-year quarter. The increase was due to higher personnel-related and professional services expenses.
Net loss of $22.9 million as compared to a net income of $11.0 million for the prior-year quarter due to a decrease in related party revenue driven by the achievement of a first-patient-first-dose milestone in the first quarter of 2020 for the PLN-1474 Phase 1 trial.
As of March 31, 2021, the Company had cash, cash equivalents and short-term investments of $264.1 million. The Company believes it has sufficient funds to meet its operating and capital requirements into 2023.

On May 10, 2021 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported first quarter 2021 financial results (Press release, Precigen, MAY 10, 2021, View Source [SID1234579584]).

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"In the first quarter of 2021, our portfolio, including our most advanced clinical programs, has progressed consistent with guidance," said Helen Sabzevari, PhD, President and CEO of Precigen. "Our UltraCAR-T trials for PRGN-3005 in ovarian cancer and PRGN-3006 in acute myeloid leukemia as well as the PRGN-2009 trial in HPV-associated cancers continue to progress according to plan. We were pleased to initiate the first-in-human Phase 1 study of PRGN-2012, Precigen’s first off-the-shelf AdenoVerse immunotherapy targeting infectious disease to enter the clinic, and receive orphan drug designation from the US FDA in patients with RRP. We look forward to upcoming presentations of new clinical data for AG019 at FOCIS and the current trial status for PRGN-2009 at ASCO (Free ASCO Whitepaper) and we anticipate multiple data readouts from our portfolio in the coming months, meeting our stated milestones."

Business Highlights:

PRGN-3005 UltraCAR-T

Overview: PRGN-3005 UltraCAR-T is a first-in-class investigational therapy under evaluation in a Phase 1/1b clinical trial for the treatment of advanced, recurrent platinum resistant ovarian, fallopian tube or primary peritoneal cancer. Study subjects receive the PRGN-3005 infusion either via intraperitoneal (IP) (Arm A) or intravenous (IV) (Arm B) infusion (clinical trial identifier: NCT03907527). The study is being conducted in collaboration with the University of Washington and Fred Hutchinson Cancer Research Center. Preliminary Phase 1 data reported from the lowest two dose levels of the IP arm showed a favorable safety profile with no dose-limiting toxicities (DLTs), neurotoxicity or cytokine release syndromes (CRS); encouraging expansion and persistence without lymphodepletion; and clinical activity as evidenced by regression in total target tumor burden.
Enrollment Status: Dose escalation in both IP and IV arms of the Phase 1 trial is ongoing concurrently. Enrollment was completed in dose level 3 of the IP arm and dosing was initiated in dose level 4 of the IP arm. Escalation to higher doses is made possible as a result of the implementation of the UltraPorator system for on-site rapid manufacturing. The first patient was dosed in the IV arm after the US Food and Drug Administration (US FDA) cleared dosing of patients in the dose escalation phase of the IV arm concurrently with the IP arm. The US FDA has cleared enrollment of patients in dose level 3 in the IV arm without the need to follow 3+3 dose escalation through dose levels 1 and 2.
Upcoming Milestones: The Company anticipates the presentation of interim data from the IP arm of the Phase 1 dose escalation trial as well as the initiation of the expansion phase of the IP arm in the second half of 2021.
PRGN-3006 UltraCAR-T

Overview: PRGN-3006 UltraCAR-T is a first-in-class investigational therapy currently under evaluation in a Phase 1/1b clinical trial for the treatment of patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) or higher-risk myelodysplastic syndromes (MDS). Study subjects receive the PRGN-3006 infusion either without prior lymphodepletion (Cohort 1) or following lymphodepleting chemotherapy (Cohort 2) (clinical trial identifier: NCT03927261). The study is being conducted in collaboration with the H. Lee Moffitt Cancer Center & Research Institute. PRGN-3006 UltraCAR-T has been granted Orphan Drug Designation in patients with AML by the US FDA. Preliminary Phase 1 data reported for the two lowest dose levels in Cohort 1 and the lowest dose level in Cohort 2 showed a favorable safety profile with no DLTs or neurotoxicity; encouraging expansion and persistence of PRGN-3006 UltraCAR-T in both cohorts; and clinical activity as evidenced by reduction in AML tumor blast levels. One of the patients treated with PRGN-3006 at the lowest dose level with lymphodepletion (Cohort 1), with approximately nine million UltraCAR-T cells, achieved complete remission with incomplete hematologic recovery (CRi) per European Leukemia Net (ELN) criteria.
Enrollment Status: The dose escalation phase of both the lymphodepletion and non-lymphodepletion cohorts of the Phase 1 trial is ongoing concurrently. Enrollment was completed in dose level 3 of the non-lymphodepletion cohort and dose level 2 of the lymphodepletion cohort.
Upcoming Milestones: The Company anticipates the presentation of interim Phase 1 data as well as the initiation of the dose expansion phase in the second half of 2021.
AG019 ActoBiotics

Overview: AG019 ActoBiotics is a first-in-class, orally administered, investigational therapy designed to address the underlying cause of Type 1 diabetes (T1D) and is currently under evaluation in a Phase 1b/2a clinical trial for the treatment of early-onset T1D (clinical trial identifier: NCT03751007; EudraCT 2017-002871-24). Interim data from both the Phase 1b monotherapy and Phase 2a combination arms showed a favorable safety profile with no dose-related adverse events or serious adverse events; an encouraging trend in insulin C-peptide levels, a biomarker for T1D disease progression; an increase in preproinsulin (PPI)-specific Type 1 regulatory (Tr1) cells; and a decrease in PPI specific CD8+ T cells.
Enrollment Status: Enrollment and dosing is complete in the Phase 1b and Phase 2a portions of the study.
Clinical Data Presentation at FOCIS 2021: Interim data from the AG019 Phase 1b/2a clinical trial will be presented on June 10, 2021 at 2:05 PM PT as an oral presentation at the Federation of Clinical Immunology Societies (FOCIS) 2021 Virtual Annual Meeting. The abstract entitled, "Lactococcus lactis producing Proinsulin and IL-10 therapy increases Antigen Specific Regulatory T-cells in Monotherapy and in Combination with an anti-CD3 Monoclonal Antibody (Teplizumab) in newly diagnosed T1D patients" will be presented by Kevan Herold, MD, CNH Long Professor of Immunobiology and of Medicine (Endocrinology) at the Yale School of Medicine.
PRGN-2009 AdenoVerse Immunotherapy

Overview: PRGN-2009 is a first-in-class, off-the-shelf (OTS) investigational immunotherapy utilizing the AdenoVerse platform designed to activate the immune system to recognize and target HPV-positive (HPV+) solid tumors. PRGN-2009 is currently under evaluation in a Phase 1/2 clinical trial as a monotherapy or in combination with bintrafusp alfa (M7824) in patients with HPV-associated cancers (clinical trial identifier: NCT04432597). The study is being conducted under a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI). Preliminary Phase 1 data from the monotherapy arm of the Phase 1 trial showed that all patients (n=6) received multiple PRGN-2009 administrations and repeated administration of PRGN-2009 treatment was well-tolerated with no DLTs. Preliminary correlative analysis from patients treated with PRGN-2009 monotherapy at dose level 1 (n=3) demonstrated an increase in HPV 16 and/or HPV 18-specific T-cell response post PRGN-2009 administration in 100% (3 of 3) of patients and an increase in the magnitude and breadth of immune response was seen with repeated administrations of PRGN-2009.
Enrollment Status: The Phase 1 monotherapy arm has completed enrollment. Subsequently, the Phase 2 trial in patients with newly diagnosed stage II/III p16-positive oropharyngeal cancer or patients with newly diagnosed operable stage II/III/IVA/IVB HPV+ sinonasal squamous cell cancer was initiated. The first patient in the Phase 2 trial was dosed.
Preclinical Data Publication: Preclinical data for PRGN-2009 was published in the Journal of Clinical Investigation entitled, "Characterization of recombinant gorilla adenovirus HPV therapeutic vaccine PRGN-2009," which provides the first evaluation of PRGN-2009 and shows promising preclinical antitumor efficacy and induction of HPV-specific T cells, along with the rationale for its evaluation in clinical trials.
Trial-in-Progress Presentation at ASCO (Free ASCO Whitepaper) 2021: A trial-in-progress update on the PRGN-2009 study will be provided at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 annual meeting. The abstract entitled, "First-in-human Phase 1/2 trial of PRGN-2009 vaccine as monotherapy or with bintrafusp alfa in patients with recurrent/metastatic (R/M) human papillomavirus (HPV)-associated cancers (HPVC) and as neoadjuvant/induction therapy in locoregionally advanced (LA) HPV oropharyngeal (OP) and sinonasal (SN) squamous cell cancer (SCC)" will be presented as a poster presentation by Charalampos S. Floudas, MD, DMSc, MS, Assistant Research Physician, Genitourinary Malignancies Branch at the Center for Cancer Research at the NCI.
Upcoming Milestones: The Company anticipates the presentation of interim Phase 1 data in the second half of 2021.
PRGN-2012 AdenoVerse Immunotherapy

Overview: PRGN-2012 is a first-in-class, investigational OTS AdenoVerse immunotherapy designed to elicit immune responses directed against cells infected with HPV 6 or HPV 11 for treatment of recurrent respiratory papillomatosis (RRP). A Phase 1 clinical trial of PRGN-2012 AdenoVerse immunotherapy in adult patients with RRP is ongoing (clinical trial identifier: NCT04724980). In preclinical studies, PRGN-2012 showed robust HPV 6 and HPV 11-specific T-cell responses in RRP patient samples in vitro.
Orphan Drug Designation: In March 2021, the Company received US FDA Orphan Drug Designation for PRGN-2012 AdenoVerse immunotherapy in patients with RRP.
Enrollment Status: In March 2021, the first patient was dosed in the Phase 1 study.
First Quarter 2021 Financial Highlights

Net cash used in operating activities of $16.4 million in 2021 compared to $27.7 million in 2020;
Cash, cash equivalents, short-term and long-term investments totaled $209.3 million as of March 31, 2021; and
Total revenues of $24.5 million in 2021 compared to $29.8 million in 2020.
First Quarter 2021 Financial Results Compared to Prior Year Period
Research and development expenses decreased $0.8 million, or 7%, from the quarter ended March 31, 2020. Salaries, benefits, and other personnel costs decreased $0.7 million in 2021 as the Company scaled down certain research and development functions in the first quarter of 2020 as a result of certain programs being previously deprioritized. Selling, general and administrative expenses decreased $2.8 million, or 13%. Salaries, benefits, and other personnel costs decreased $1.0 million in 2021 primarily due to a reduced headcount as the Company scaled down its corporate functions to support its more streamlined organization and reduced stock compensation costs for previously granted awards that became fully vested in early 2021. Professional fees decreased $1.0 million primarily due to a decrease in legal fees associated with certain litigation matters that were settled in the second half of 2020. Net loss from continuing operations was $21.8 million, or $(0.11) per basic share, of which $9.7 million was for non-cash charges in 2021 compared to net loss from continuing operations of $20.8 million, or $(0.13) per basic share, of which $7.7 million was for non-cash charges in 2020.

Total revenues decreased $5.3 million, or 18%, from the quarter ended March 31, 2020. Collaboration and licensing revenues decreased $10.7 million primarily due to the recognition of previously deferred revenue upon the mutual termination of one of its collaboration agreements in February 2020. Product and service revenues generated by Trans Ova and Exemplar increased $5.4 million primarily due to higher customer demand for Trans Ova’s products and services as a result of stronger beef and dairy industries in the current year, as well as increased services provided by Exemplar to new and existing customers. Gross margin on products and services improved as a result of the increased revenues, a change in pricing structure for certain customers, and operational efficiencies that have been gained through reductions in workforce and improved inventory management.