On August 9, 2022 Foghorn Therapeutics Inc. (Nasdaq: FHTX), a clinical stage biotechnology company pioneering a new class of medicines that modulate gene expression through selectively targeting the chromatin regulatory system, today provided a financial and corporate update in conjunction with the Company’s 10-Q filing for the quarter ended June 30, 2022 (Press release, Foghorn Therapeutics, AUG 9, 2022, View Source [SID1234617935]). With an initial focus in oncology, Foghorn’s Gene Traffic Control Platform and resulting broad pipeline has the potential to transform the lives of people suffering from a wide spectrum of diseases.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"During the second quarter, supported by a strong balance sheet, Foghorn continued to advance its broad and deep pipeline of more than a dozen highly differentiated programs while making important progress towards our goal of becoming a fully integrated biotech company," said Foghorn CEO Adrian Gottschalk. "We continue to enroll patients in the Phase 1 dose escalation study of FHD-286 in uveal melanoma and FHD-609 in synovial sarcoma, and we have been working diligently to resolve the partial clinical hold of FHD-286 in AML and MDS. In addition, we are pleased with the continued progress with our Merck collaboration, and in particular, the achievement of the first research milestone."

Key Recent Updates

FHD-286 AML/MDS Update. In May, the Food and Drug Administration (FDA) placed the Phase 1 dose escalation study of FHD-286 in relapsed and/or refractory acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) on a partial clinical hold. The partial clinical hold was initiated by the FDA following the report of a recent death that occurred in a subject with potential differentiation syndrome. Differentiation syndrome is associated with AML/MDS therapeutics that induce differentiation, an effect that is believed to be on-target for the proposed mechanism of action for FHD-286. The Company continues to work to resolve the partial clinical hold with the FDA.

FHD-286 mUM Update. The dose escalation Phase 1 study in metastatic uveal melanoma (mUM) continues to enroll patients per protocol. The partial clinical hold does not apply to this study of FHD-286.

FHD-609 Update. Patient enrollment is continuing in the Phase 1 dose escalation clinical study of FHD-609, a potent and selective heterobifunctional protein degrader of BRD9, initially being developed for the treatment of synovial sarcoma with initial data expected in 2023.

Merck Collaboration Update. In July 2022, a research milestone was achieved under the Merck collaboration triggering a $5 million milestone payment to Foghorn which will be reflected in the quarter ended September 30, 2022 financials.

BRM-selective Progress. Foghorn is advancing its BRM-selective programs in collaboration with Loxo@Lilly, with the BRM-selective inhibitor program in lead optimization and the protein degrader program in hit-to-lead stage. Foghorn is leading discovery and early research activities, and Lilly is leading development and commercialization activities with participation from Foghorn. U.S. economics will be shared equally, and Foghorn is eligible to receive royalties on ex-U.S. sales in the low double-digit to twenties range based on revenue levels.

Pipeline Advancement. Foghorn continued to advance its broad therapeutic pipeline of which the majority are wholly owned, including protein degraders, enzymatic inhibitors and transcription factor disruptors targeting cancers impacted by breakdowns in the chromatin regulatory system. We continue to invest in our protein degradation capabilities with approximately half of our pipeline programs utilizing this modality. This investment includes our protein degrader asset, ARID1B, for which we have identified several different biophysically validated chemical scaffolds.

Second Quarter 2022 Financial Highlights

Strong Balance Sheet and Cash Runway. As of June 30, 2022, the Company had $394.7 million in cash, cash equivalents and marketable securities.
Collaboration Revenues. Collaboration revenues were $4.5 million for the second quarter of 2022 compared to $0.3 million the second quarter of 2021. The increase was driven by revenue recognized under the Lilly Collaboration Agreement which was entered into in December 2021.
Research and Development Expenses. Research and development expenses were $26.0 million for the second quarter of 2022 compared to $18.6 million for the second quarter of 2021. This increase was primarily due to costs associated with the Phase 1 studies for both FHD-286 and FHD-609, which were initiated in 2021, and continued investment in R&D personnel, the platform and other early-stage research.

General and Administrative Expenses. General and administrative expenses were $7.7 million for the second quarter of 2022, compared to $4.9 million for the second quarter of 2021. This increase was primarily due to an increase in headcount to support the growing business.

Net Loss. Net loss was $27.3 million for the second quarter of 2022 compared to a net loss of $23.1 million for the second quarter of 2021.

About FHD-286

FHD-286 is a highly potent, selective, allosteric and orally available, small-molecule, enzymatic inhibitor of BRG1 and BRM, two highly similar proteins that are the ATPases, or the catalytic engines across all forms of the BAF complex, one of the key regulators of the chromatin regulatory system. In preclinical studies, FHD-286 has shown anti-tumor activity across a broad range of malignancies including both hematologic and solid tumors. To learn more about these studies please visit ClinicalTrials.gov. (Link here for metastatic uveal melanoma and here for AML and MDS).

About AML

Adult acute myeloid leukemia (AML) is a cancer of the blood and bone marrow and the most common type of acute leukemia in adults. AML is a diverse disease associated with multiple genetic mutations. It is diagnosed in about 20,000 people every year in the United States.

About Uveal Melanoma

Uveal (intraocular) melanoma (UM) is a rare eye cancer that forms from cells that make melanin in the iris, ciliary body and choroid. It is the most common eye cancer in adults. It is diagnosed in about 2,000 adults every year in the United States and occurs most often in lightly pigmented individuals with a median age of 55 years. However, it can occur in all races and at any age. UM metastasizes in approximately 50% of cases, leading to very poor prognosis.

About FHD-609

FHD-609 is a potent, selective, intravenously administered protein degrader of BRD9, a component of the ncBAF complex. Preclinical studies have demonstrated tumor growth inhibition in synovial sarcoma, a cancer genetically dependent on BRD9. To learn more about the first-in-human clinical trial of FHD-609 in synovial sarcoma, please visit ClinicalTrials.gov.

About Synovial Sarcoma

Synovial sarcoma is a rare, often aggressive soft tissue sarcoma that originates from different types of soft tissue, including muscle or ligaments. Synovial sarcoma can occur at any age but is most common among adolescents and young adults. It represents around 5-10% of all soft tissue sarcomas, with ~800 new cases each year in the United States. Surgery remains the most effective treatment for synovial sarcoma, and there are limited therapeutic treatment options.

On August 8, 2022 TG Therapeutics, Inc. (NASDAQ: TGTX) reported its financial results for the second quarter ended June 30, 2022 and recent company developments, along with a business outlook for the remainder of 2022 (Press release, Manhattan Pharmaceuticals, AUG 8, 2022, View Source [SID1234617741]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Michael S. Weiss, the Company’s Chairman and Chief Executive Officer, stated, "Our primary focus for the remainder of this year is working toward the approval of ublituximab, which has a PDUFA goal date of December 28, 2022, and preparing for its potential launch in early 2023. If approved, we believe ublituximab has the potential to be a meaningful treatment option for patients with relapsing forms of multiple sclerosis." Mr. Weiss continued, "During the first half of the year we implemented a number of cost-saving measures, and we are pleased to report those efforts have resulted in a lower than expected 2Q burn, which we believe puts us in a good financial position as we approach the potential launch of ublituximab."

Recent Highlights

Ublituximab in Multiple Sclerosis

●U.S. Food and Drug Administration (FDA) accepted the Biologics License Application (BLA) for ublituximab, as a treatment for patients with relapsing forms of multiple sclerosis (RMS) and set a Prescription Drug User Fee Act (PDUFA) goal date of December 28, 2022.
●Presented new exploratory analyses, from the ULTIMATE I and II Phase 3 trials at the 2022 Consortium of Multiple Sclerosis Centers Annual Meeting (CMSC) and the 8th Congress of the European Academy of Neurology (EAN). As previously reported, both trials met their primary endpoint with ublituximab treatment demonstrating a statistically significant reduction in annualized relapse rate (ARR) over a 96-week period compared to teriflunomide in patients with RMS.

Key Objectives for 2022

●Obtain FDA approval of ublituximab to treat relapsing forms of multiple sclerosis by the PDUFA goal date of December 28, 2022
●Strengthen our commercial infrastructure to support the potential launch of ublituximab

Financial Results for the Three and Six Months Ended June 30, 2022

●Net Loss: Net loss was $40.5 million and $109.5 million for the three and six months ended June 30, 2022, respectively, compared to $78.5 million and $169.1 million for the three and six months ended June 30, 2021. The decrease in net loss in both periods is primarily the result of our cost-savings measures implemented and the withdrawal of UKONIQ from the market.
●R&D Expenses: Total research and development (R&D) expense was $26.9 million and $74.9 million for the three and six months ended June 30, 2022, respectively, compared to $44.9 million and $108.0 million for the three and six months ended June 30, 2021, respectively. The decrease was due primarily to decreases in licensing milestone fees, clinical trial expenses and non-cash compensation R&D expense during the three and six months ended June 30, 2022.
●SG&A Expenses: Total selling, general and administrative (SG&A) expense was $12.6 million and $33.2 million for the three and six months ended June 30, 2022, respectively, compared to $34.0 million and $60.8 million for the three and six months ended June 30, 2021, respectively. The decrease was due primarily to decreased selling, general and administrative costs, including personnel, associated with withdrawal of UKONIQ during the three and six months ended June 30, 2022. We expect our selling, general and administrative expenses to increase slightly for the remainder of 2022 as we prepare for the potential launch of ublituximab in RMS.
●Cash Position and Financial Guidance: Cash, cash equivalents and investment securities were $231.8 million as of June 30, 2022, which the Company believes will be sufficient to fund the Company’s planned operations into the second half of 2023.
CONFERENCE CALL INFORMATION

The Company will host a conference call today, August 8, 2022, at 8:30 AM ET, to discuss the Company’s second quarter 2022 financial results.

In order to participate in the conference call, please call 1-877-407-8029 (U.S.), 1-201-689-8029 (outside the U.S.), Conference Title: TG Therapeutics. A live audio webcast will be available on the Events page, located within the Investors & Media section, of the Company’s website at View Source An audio recording of the conference call will also be available for replay at www.tgtherapeutics.com, for a period of 30 days after the call.

On August 8, 2022 (GLOBE NEWSWIRE) — Chinook Therapeutics, Inc. (Nasdaq: KDNY), a biopharmaceutical company focused on the discovery, development and commercialization of precision medicines for kidney diseases, reported financial results for the quarter and six months ended June 30, 2022 (Press release, Aduro Biotech, AUG 8, 2022, View Source [SID1234617775]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"During the second quarter of 2022, we executed well on advancing our pipeline of clinical and preclinical programs for rare, severe chronic kidney diseases. We continue to ramp up enrollment of patients in the phase 3 ALIGN trial for atrasentan, and the data we presented at ERA from the ongoing phase 2 AFFINITY trial of atrasentan demonstrated consistent and clinically meaningful proteinuria reductions in patients with IgAN," said Eric Dobmeier, president and chief executive officer of Chinook Therapeutics. "For BION-1301, the additional data presented at ERA from the ongoing phase 1/2 trial reaffirms its disease-modifying potential in IgAN by demonstrating durable reductions in mechanistic biomarkers and corresponding impressive proteinuria reductions. We look forward to advancing BION-1301 into a phase 3 study for patients with IgAN in 2023. We are also continuing to make progress with dose escalation in the ongoing phase 1 trial of CHK-336 in healthy volunteers and expect to report data in the first half of 2023."

Recent Accomplishments and Updates

Atrasentan
Atrasentan is a potent and selective endothelin A (ETA) receptor antagonist that has the potential to provide benefit in multiple chronic kidney diseases by reducing proteinuria and having direct anti-inflammatory and anti-fibrotic effects to preserve kidney function. The phase 3 ALIGN trial of atrasentan is currently enrolling patients with IgAN, and the phase 2 AFFINITY basket trial of atrasentan is currently enrolling patients with proteinuric glomerular diseases.

Enrollment of the phase 3 ALIGN trial of atrasentan continues to advance with the activation of new trial sites and expansion into additional countries. Chinook expects to report topline data from the six-month interim proteinuria endpoint analysis in 2023 to support an application for accelerated approval under Subpart H in the United States.

Chinook presented data from the IgAN patient cohort of the phase 2 AFFINITY trial in an oral presentation at the 59th ERA Congress in May 2022, demonstrating consistent and clinically meaningful proteinuria reductions at weeks six, 12 and 24 of treatment in patients with IgAN already on a maximally tolerated and stable dose of a RAS inhibitor. Specifically, atrasentan demonstrated a 38.0% geometric mean reduction in 24-hour urine protein creatinine ratio (UPCR) in 20 patients at six weeks of treatment, 49.9% geometric mean reduction in 24-hour UPCR in 18 patients at 12 weeks of treatment and 58.5% geometric mean reduction in 24-hour UPCR in 11 patients at 24 weeks of treatment. After 24 weeks of treatment, ten of the 11 patients (91%) who had completed this visit had greater than a 40% cumulative reduction in UPCR. There were no meaningful changes in blood pressure or acute eGFR effects, suggesting proteinuria reductions were not primarily due to hemodynamic effects of atrasentan. There were no increases in BNP or mean bodyweight, suggesting minimal fluid retention. As of the April 22, 2022 data cutoff, atrasentan was well-tolerated in patients with IgAN, with no treatment-related serious adverse events.

Chinook has completed enrollment of the IgAN patient cohort of the AFFINITY trial, and continues to enroll the other three cohorts, including patients with focal segmental glomerulosclerosis (FSGS), Alport syndrome and diabetic kidney disease in combination with SGLT2 inhibitors. Chinook plans to report additional data from the AFFINITY trial in the second half of 2022, as well as during 2023.

Chinook delivered a mini-oral presentation at the 59th ERA Congress on preclinical mechanistic data describing atrasentan’s effect to block mesangial cell injury and the pathogenic transcriptional networks driving IgAN progression in a model system.
BION-1301
BION-1301 is a novel anti-APRIL monoclonal antibody currently in phase 1/2 development for patients with IgAN. BION-1301’s potentially disease-modifying approach to treating IgAN by reducing circulating levels of galactose-deficient IgA1 (Gd-IgA1) to prevent the formation of pathogenic immune complexes has been demonstrated preclinically as well as clinically in both healthy volunteers and patients with IgAN.

Enrollment of up to 30 patients in Cohort 2 of Part 3 of the ongoing phase 1/2 trial of BION-1301 is ongoing. Patients in Cohort 2 receive a SC dose of 600 mg of BION-1301 every two weeks. Chinook expects to report initial data from Cohort 2 in the second half of 2022.

Based on the data generated to date in the ongoing phase 1/2 study and after consulting with an expert advisory panel, Chinook has decided to advance BION-1301 into phase 3 utilizing the current Cohort 2 dose of 600 mg SC every two weeks, and will not move forward with the optional Cohort 3. Chinook is currently finalizing trial design, conducting site and country feasibility and pursuing regulatory interactions to enable initiation of a global phase 3 trial of BION-1301 in 2023.

Chinook presented additional interim data from Cohort 1 of Part 3 in a mini-oral presentation at the ERA Congress in May 2022, further demonstrating its disease-modifying potential in IgAN by generating durable reductions in mechanistic biomarkers and corresponding impressive proteinuria reductions within three months of initiating treatment. After at least 24 weeks of treatment, patients in Cohort 1 transitioned from IV dosing at 450 mg every two weeks to SC dosing at 600 mg every two weeks. BION-1301 treatment resulted in steady-state reductions in Gd-IgA1 in the range of 70–80%, demonstrating depletion of the pathogenic IgA variant, and establishing the potentially disease-modifying mechanism of BION-1301 by directly targeting the initial pathway in the pathogenesis of IgAN. Additionally, BION-1301 demonstrated a 48.8% geometric mean reduction in 24-hour UCPR in all eight patients at six months of treatment, a 70.9% geometric mean reduction in 24-hour UPCR in six patients at one year of treatment and a 69.1% geometric mean reduction in 24-hour UPCR in two patients at 1.5 years of treatment. As of the May 6, 2022 data cutoff, BION-1301 was well-tolerated, with no serious adverse events or treatment discontinuations due to adverse events.

BION-1301 was granted orphan drug designation for the treatment of primary IgAN by the European Commission in July 2022.
CHK-336
CHK-336 is an oral small molecule lactate dehydrogenase A (LDHA) inhibitor with liver-targeted tissue distribution that Chinook is developing for the treatment of patients with primary hyperoxaluria (PH), secondary hyperoxaluria due to increased endogenous oxalate production and idiopathic stone formation.

In April 2022, Chinook initiated dosing in a phase 1 clinical trial evaluating CHK-336 in healthy volunteers. Data from this trial is expected in the first half of 2023.
Precision Medicine Research & Discovery
Chinook is focused on the discovery and development of novel precision medicines for rare, severe chronic kidney diseases (CKDs) with defined genetic or molecular drivers of disease initiation and progression, and efficient development paths. Chinook has multiple preclinical programs across the discovery, target validation, lead identification and lead optimization stages to generate future clinical pipeline candidates. Chinook is leveraging its ongoing strategic collaboration with Evotec to identify and validate novel targets and enable patient stratification strategies through access to the NURTuRE CKD Patient Biobank, which provides comprehensive PANOMICS characterization of thousands of CKD patients with prospective clinical follow-up and retained bio-samples of urine and blood for exploratory biomarker analysis.

Chinook delivered an oral presentation at the 59th ERA Congress in May 2022 on the approach used in collaboration with Evotec to leverage the NURTuRE CKD biobank to generate mechanistic disease understanding for patient-centric, integrated target and biomarker discovery that will enable the development of novel precision treatments for CKD patient subsets.
Corporate

In May 2022, Chinook completed an underwritten public offering of 7.6 million shares of common stock at a price to the public of $14.00 per share, including the exercise in full of the underwriters’ option to purchase an additional 1.1 million shares of common stock. As part of the offering, Chinook sold to certain investors pre-funded warrants to purchase up to an aggregate of 1.1 million shares of common stock at a purchase price of $13.9999 per pre-funded warrant. The underwritten public offering resulted in gross proceeds to Chinook of $120.7 million.

In April 2022, Chinook announced an outreach initiative in collaboration with the IgA Nephropathy Foundation and Komodo Health, leveraging data and technology to drive awareness of IgAN and engage key medical providers at nephrology practices across the U.S., with the goal of ensuring patients have access to optimal support and treatment options earlier in their disease journey.
Quarter and Six Months Ended June 30, 2022 Financial Results

Cash Position – Cash, cash equivalents and marketable securities totaled $405.2 million at June 30, 2022, compared to $355.1 million at December 31, 2021.

Revenue – Revenue for the quarter and six months ended June 30, 2022 was $0.4 million and $3.1 million, respectively, compared to less than $0.1 million and $0.4 million for the same periods in 2021. The increase was primarily due to revenue recognized under Chinook’s license agreement with SanReno.

Expenses –

Research and development expenses for the quarter and six months ended June 30, 2022 were $30.0 million and $56.3 million, respectively, compared to $22.8 million and $48.5 million, respectively, for the same periods in 2021. The increase was primarily due to higher employee-related costs, including stock-based compensation expense, consulting and outside services fees, as well as facilities and other costs to continue progression of our research and clinical programs. The increase in the three months ended June 30, 2022 also included an increase in licensing and contract research and manufacturing costs. The increase in the six months ended June 30, 2022, was partially offset by a decrease resulting from an upfront fee of $3.3 million to Evotec International GmbH recognized in the same period in 2021.
General and administrative expenses for the quarter and six months ended June 30, 2022 were $8.6 million and $16.5 million, respectively, compared to $7.8 million and $17.3 million, respectively, for the same periods in 2021. The increase during the quarter ended June 30, 2022 was primarily due to higher consulting and outside services costs to support our operations and an increase in stock-based compensation expense, partially offset by lower facilities and other costs. The decrease during the six months ended June 30, 2022 was primarily due to lower employee-related costs and facilities and other costs, partially offset by an increase in stock-based compensation expense.

The change in fair value of contingent consideration and contingent value rights liabilities for the quarter and six months ended June 30, 2022 was a benefit of $2.0 million and $3.0 million, respectively, compared to expense of $19.6 million and $21.4 million for the same periods in 2021. The decrease in these non-cash expenses was primarily due to a change in the fair value in the second quarter of 2021 to include the impact of Merck intending to evaluate MK-5890 in a phase 2 clinical study for a new indication and the sale of certain of our non-renal assets in exchange for preferred shares in Sairopa B.V.

Other –

A $10.0 million development milestone under the Merck collaboration was earned in the fourth quarter of 2021 and received in the first quarter of 2022. We paid this milestone, net of taxes and expenses, to the CVR holders in the second quarter of 2022.

Net Loss – Net loss for the quarter and six months ended June 30, 2022 was $37.6 million, or $0.61 per share, and $69.3 million, or $1.15 per share, respectively. Net loss for the quarter and six months ended June 30, 2021 was $42.6 million, or $0.97 per share, and $79.8 million, or $1.86 per share, respectively.

On August 8, 2022 Terns Pharmaceuticals, Inc. ("Terns" or the "Company") (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology, obesity and non-alcoholic steatohepatitis (NASH), reported financial results for the second quarter ended June 30, 2022 and corporate highlights (Press release, Terns Pharmaceuticals, AUG 8, 2022, View Source [SID1234617791]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"During the second quarter, Terns saw significant progress in advancing three of our internally discovered, small-molecule product candidates towards key clinical readouts in chronic myeloid leukemia, obesity and NASH," said Sen Sundaram, chief executive officer at Terns. "We look forward to assessing the differentiation of these three product candidates, each of which target clinically validated mechanisms of action."

Recent Developments and Anticipated Milestones

TERN-701: Oral, allosteric BCR-ABL tyrosine kinase inhibitor (TKI) for chronic myeloid leukemia

In May 2022, Hansoh Pharmaceutical Group Company Limited (Hansoh) initiated dosing of TERN-701 in a Phase 1 dose-escalation and dose-expansion trial in approximately 100 patients with CML (NCT05367700)
The objectives of this trial are to evaluate the tolerability, efficacy, and pharmacokinetics of TERN-701 in CML
TERN-701 is Terns’ proprietary, allosteric BCR-ABL TKI, designed to target the ABL myristoyl pocket, for the treatment of chronic myeloid leukemia (CML)
TERN-701 aims to address limitations of the only FDA-approved allosteric BCR-ABL TKI with the goal of achieving improved tumor suppression through a combination of: (1) potent activity against CML including a broad range of mutations, (2) improved PK to enable potential once-daily dosing, and (3) minimal food or fasting requirements
TERN-701 is out-licensed to Hansoh for development in the greater China region. Hansoh is responsible for all development costs in China, including the ongoing Phase 1 trial
Terns retains all worldwide development and commercialization rights outside of greater China, as well as access to data generated by Hansoh in China
Terns is exploring options for the development and commercialization of TERN-701 outside of China, including potential internal development and/or additional strategic partnerships
TERN-601: Oral, small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist for obesity

IND-enabling activities for TERN-601, Terns’ lead GLP-1R development candidate, are proceeding on-track with the goal of initiating a first-in-human clinical trial in 2023
The Phase 1 clinical program for TERN-601 is expected to include a single ascending dose trial and a multiple ascending dose proof-of-concept trial assessing potential endpoints such as body weight and HbA1c
TERN-601 is a Terns’ proprietary orally-administered small-molecule glucagon-like peptide-1 receptor (GLP-1R) agonist for the treatment of obesity
Terns screened more than 20,000 molecular permutations through its proprietary quantitative structure activity relationship (QSAR) model to identify suitable small-molecule scaffolds with potentially improved properties relative to other GLP-1-based approaches
Terns has identified structures believed to be suitable for oral administration as a single-agent or in combination with other drug candidates within its pipeline
TERN-501: Oral, thyroid hormone receptor-beta (THR-β) agonist for NASH

In July 2022, Terns initiated dosing in the DUET Phase 2a clinical trial of TERN-501 (THR-β agonist) alone and in combination with TERN-101 (FXR agonist) in approximately 140 adult patients with presumed NASH (NCT05415722)
Primary endpoint is the relative change from baseline in liver fat content as measured by MRI-PDFF at Week 12 for TERN-501 monotherapy compared with placebo
Secondary endpoints include assessment of changes in MRI-PDFF (combination vs. placebo) and MRI cT1 (TERN-501 monotherapy vs. placebo as well as 501+101 combination vs. placebo)
Top-line data expected in the second half of 2023
Key Appointments

Radhika Tripuraneni, M.D., M.P.H. joined the Company’s Board of Directors in July 2022. Dr. Tripuraneni serves as the Chief Development Officer of Prothena Corporation plc and brings to the Terns Board of Directors more than 15 years of experience in drug development
Kerry Russell, M.D., Ph.D. joined the Company as Chief Medical Officer in June 2022. Dr. Russell was most recently vice president of late clinical development at Dicerna Pharmaceuticals, Inc. and was previously an associate professor at Yale University School of Medicine for over 13 years
Upcoming Investor Events

Terns will present at the Canaccord Genuity 42nd Annual Growth Conference on Thursday, August 11, 2022 at 11:30am ET. A live webcast of the event will be available on the investor relations page of the Terns Pharmaceuticals website at View Source A replay of the webcast will be archived on Terns’ website for 30 days following the presentation.
Second Quarter 2022 Financial Results

Cash Position: As of June 30, 2022, cash, cash equivalents and marketable securities were $139.8 million as compared with $166.0 million as of December 31, 2021. Based on its current operating plan, Terns expects these funds will be sufficient to support its planned operating expenses into 2025, including through the expected proof-of-concept clinical readouts for TERN-701, TERN-601 and TERN-501

Research and Development (R&D) Expenses: R&D expenses were $8.7 million for the quarter ended June 30, 2022, as compared with $6.0 million for the quarter ended June 30, 2021

General and Administrative (G&A) Expenses: G&A expenses were $5.4 million for the quarter ended June 30, 2022, as compared with $4.9 million for the quarter ended June 30, 2021

Net Loss: Net loss was $13.9 million for the quarter ended June 30, 2022, as compared with $10.7 million for the quarter ended June 30, 2021

On August 8, 2022 Reata Pharmaceuticals, Inc. (Nasdaq: RETA) ("Reata," the "Company," "our," "us," or "we"), a clinical-stage biopharmaceutical company, reported financial results for the second quarter of 2022 and provided an update on the Company’s business operations and clinical development programs (Press release, Reata Pharmaceuticals, AUG 8, 2022, View Source [SID1234617806]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Recent Company Highlights

Omaveloxolone in Patients with Friedreich’s Ataxia

Following the announcement of the positive data from the MOXIe Part 2 study in October 2019, the U.S. Food and Drug Administration ("FDA") stated that it did not have any concerns with the reliability of the modified Friedreich’s ataxia rating scale ("mFARS") primary endpoint results in the MOXIe Part 2 study and requested additional evidence of persuasiveness to support a New Drug Application ("NDA") filing. We then began a series of interactions with the FDA to provide additional evidence of effectiveness to support a single study approval. This ultimately led to a pre-NDA meeting and subsequent NDA submission in March 2022 after FDA’s review of our Delayed-Start Analysis, which it had requested.

In May 2022, the FDA accepted for filing our NDA for omaveloxolone for the treatment of patients with Friedreich’s ataxia and granted Priority Review. The FDA has granted Fast Track Designation, Orphan Drug Designation, and Rare Pediatric Disease Designation to omaveloxolone for the treatment of Friedreich’s ataxia. The FDA advised us that it is planning to hold an advisory committee meeting to discuss the application, and our application has been assigned a Prescription Drug User Fee Act ("PDUFA") target action date of November 30, 2022.

We recently completed a mid-cycle communication meeting with the FDA. The purpose of the mid-cycle communication meeting is for the FDA to provide the sponsor with an update of the status of the NDA review, including any issues identified. While we have not received formal minutes from the FDA, in the preliminary agenda for, and during, the mid-cycle communication meeting, the FDA stated that it has not identified any new significant issues, but it continues to have concerns regarding the strength of the efficacy evidence. The FDA did not identify any significant clinical safety issues. The FDA stated that the safety review is ongoing, and they are continuing to evaluate the cardiac safety of omaveloxolone in patients with Friedreich’s ataxia. They have not identified any other major safety concerns at this stage of their review.

During the mid-cycle meeting, we proposed to address FDA’s concerns in three ways. First, we presented updated results from the Delayed-Start Analysis using a March 2022 data cut-off, which contain new, later time points and increased numbers of patients at later time points than the prior analysis. Second, we proposed to submit a new propensity-matched matched analysis of MOXIe Extension data using the largest, most robust Friedreich’s ataxia natural history study to provide additional clinical data that could be considered confirmatory evidence. Third, we discussed an additional NDA amendment containing compelling mechanistic evidence in the setting of Friedreich’s ataxia’s well-understood disease pathophysiology, which could also serve as confirmatory evidence. The FDA acknowledged these data and agreed that we could submit the updated data to the NDA. We have submitted the following additional data and analyses to the FDA.

Results from March 2022 Data Cut-Off of MOXIe Extension

Results of the updated Delayed-Start Analysis from the March 2022 data cut-off demonstrated that the between-group difference in mFARS observed at the end of the placebo-controlled MOXIe Part 2 treatment period (LS mean difference = -2.17 ± 1.09) was preserved at MOXIe Extension Week 72 in the delayed-start period (LS mean difference = -2.91 ± 1.44). Consistent with a persistent treatment effect on disease, the upper limit of the 90% Confidence Interval ("CI") for the difference estimate was less than zero (-0.09), meeting the threshold for demonstrating significant evidence of non-inferiority. Additionally, the between group difference in mFARS was maintained at Extension Week 96, 120, and 144 (LS mean difference = -2.19 ± 1.38, -2.74 ± 1.26, and -2.58 ± 1.47 respectively), and the threshold for non-inferiority was met at Extension Week 120 with an upper limit of the 90% CI of -0.106.

Post Hoc Propensity-Matched Analysis of MOXIe Extension

We recently completed a post hoc analysis comparing the mFARS progression of omaveloxolone-treated patients in the open-label MOXIe Extension trial to the progression of propensity score-matched untreated patients in the largest natural history study of Friedreich’s ataxia, Clinical Outcome Measures in Friedreich’s ataxia ("FA-COMS"). All patients enrolled in the MOXIe Extension study with at least one post-baseline assessment (n=136) were matched one to one with patients from the FA-COMS study (n=136) using five baseline characteristics, or covariates, including sex, baseline age, age of Friedreich’s ataxia onset, baseline mFARS score, and baseline gait score, which have been demonstrated to be predictive of disease progression. Demographics and baseline characteristics were highly comparable between MOXIe Extension patients and the matched FA-COMS external control group.

In the Primary Pooled Population (n=136 per group), patients in the matched FA-COMS group progressed 6.61 mFARS points at Year 3, whereas patients treated with omaveloxolone in MOXIe Extension progressed 3.00 points for a difference of -3.61 mFARS points (nominal p=0.0001). In this analysis, progression in mFARS was 55% slower in MOXIe Extension patients treated with omaveloxolone compared to matched untreated patients in the FA-COMS study.

Mechanistic Validation of Nrf2 Target Biomarkers in Friedreich’s Ataxia

We have provided additional pharmacodynamic information to the FDA including an integrated and detailed presentation of the disease pathophysiology of Friedreich’s ataxia, a review of the available pharmacodynamic data, justification of the relevance of these data in Friedreich’s ataxia and an explanation of the relationship between the mechanistic data and the observed biomarker and clinical treatment effects in patients treated with omaveloxolone. Substantial evidence demonstrates that Nrf2 levels and activity are suppressed in cells from patients with Friedreich’s ataxia and in preclinical animal models of the disease. Omaveloxolone restores Nrf2 levels and increases the expression of Nrf2 target genes, including those that encode ferritin and gamma-glutamyl transferase ("GGT"), in nonclinical models. Treatment with omaveloxolone in MOXIe Part 1 resulted in dose-dependent increases in Nrf2 activity, as assessed by serum ferritin and GGT levels. Data from MOXIe Part 2 showed an association between omaveloxolone-induced Nrf2 activity and measures of neurological function, with larger increases in Nrf2 target levels associated with larger improvements in mFARS scores.

"We look forward to continuing to work with FDA on its review of our NDA for omaveloxolone for the treatment of patients with Friedreich’s ataxia, a rare, genetic, debilitating, and degenerative neuromuscular disorder with no approved therapies," said Warren Huff, Reata’s Chief Executive Officer. "We have submitted these additional data and analyses to the FDA and are continuing to prepare for the upcoming Advisory Committee meeting."

Bardoxolone Methyl in Patients with Chronic Kidney Disease Caused by Alport Syndrome

We received a Complete Response Letter ("CRL") from the FDA in February 2022 with respect to its review of our NDA for bardoxolone methyl ("bardoxolone") in the treatment of patients with chronic kidney disease caused by Alport syndrome. The CRL indicated the FDA cannot approve the NDA in its present form. We have recently requested a Type C meeting to discuss the program and continue to work with the FDA to confirm our next steps on our Alport syndrome program.

Second Quarter Financial Highlights

Cash and Cash Equivalents

On June 30, 2022, we had cash and cash equivalents and marketable securities of $481.5 million, as compared to $590.3 million on December 31, 2021.

GAAP and Non-GAAP Research and Development ("R&D") Expenses

R&D expenses according to generally accepted accounting principles in the U.S. ("GAAP") were $39.3 million for the second quarter of 2022, as compared to $40.1 million for the same period of the year prior.

Non-GAAP R&D expenses were $33.0 million for the second quarter of 2022, as compared to $34.8 million, for the same period of the year prior.1

GAAP and Non-GAAP General and Administrative ("G&A") Expenses

GAAP G&A expenses were $25.1 million for the second quarter of 2022, as compared to $22.0 million, for the same period of the year prior.

Non-GAAP G&A expenses were $17.6 million for the second quarter of 2022, as compared to $14.0 million for the same period of the year prior.1

GAAP and Non-GAAP Net Loss

The GAAP net loss for the second quarter of 2022, was $73.6 million, or $2.02 per share, on both a basic and diluted basis, as compared to a GAAP net loss of $72.7 million, or $2.00 per share, on both a basic and diluted basis, for the same period of the year prior.

[1] See "Non-GAAP Financial Measures" below for a description of non-GAAP financial measures and a reconciliation between GAAP and non-GAAP R&D expenses, GAAP and non-GAAP G&A expenses, and GAAP and non-GAAP net loss, respectively, appearing later in the press release.

The non-GAAP net loss for second quarter of 2022, was $49.4 million, or $1.36 per share on both a basic and diluted basis, as compared to a non-GAAP net loss of $48.0 million, or $1.32 per share, on both a basic and diluted basis, for the same period of the year prior.1

Cash Guidance

The Company reaffirms its existing cash & cash equivalents and marketable debt securities will be sufficient to enable it to fund operations through the end of 2024.

Non-GAAP Financial Measures

This press release contains non-GAAP financial measures, including non-GAAP R&D expenses, non-GAAP G&A expenses, non-GAAP operating expenses, non-GAAP net loss and non-GAAP net loss per common share – basic and diluted. These measures are not in accordance with, or an alternative to, GAAP, and may be different from non-GAAP financial measures used by other companies.

The Company defines non-GAAP R&D expenses as GAAP R&D expenses, which exclude stock-based compensation expense; non-GAAP G&A expenses as GAAP G&A expenses, which exclude stock-based compensation expense; non-GAAP operating expenses as GAAP operating expenses, which exclude stock-based compensation expense; non-GAAP net loss as GAAP net loss, which excludes stock-based compensation expense and non-cash interest expense from liability related to sale of future royalties; and non-GAAP net loss per common share – basic and diluted as GAAP net loss per common share – basic and diluted, which excludes stock-based compensation expense and non-cash interest expense from liability related to sale of future royalties. The Company has excluded the impact of stock-based compensation expense, which may fluctuate from period to period based on factors including the variability associated with performance-based grants of stock options and restricted stock units and changes in the Company’s stock price, which impact the fair value of these awards. The Company has excluded the impact of accreted non-cash interest expense from liability related to sale of future royalties as it may be calculated differently from, and therefore may not be comparable to, peer companies who also provide non-GAAP disclosures. The Company has excluded the impact of stock-based compensation expense and non-cash interest expense from liability related to sale of future royalties because the Company believes its impact makes it difficult to compare its results to prior periods and anticipated future periods.

Because management believes certain items, such as stock-based compensation expense and non-cash interest expense from liability related to sales of future royalties, can distort the trends associated with the Company’s ongoing performance, the following measures are often provided, excluding special items, and utilized by the Company’s management, analysts, and investors to enhance consistency and comparability of year-over-year results, as well as to industry trends, and to provide a basis for evaluating operating results in future periods: non-GAAP net loss; non-GAAP net loss per common share – basic and diluted; non-GAAP R&D expenses; non-GAAP G&A expenses; and non-GAAP operating expenses.

The Company believes the presentation of these non-GAAP financial measures provides useful information to management and investors regarding the Company’s financial condition and results of operations. When GAAP financial measures are viewed in conjunction with these non-GAAP financial measures, investors are provided with a more meaningful understanding of the Company’s ongoing operating performance and are better able to compare the Company’s performance between periods. In addition, these non-GAAP financial measures are among those indicators the Company uses as a basis for evaluating performance, allocating resources, and planning and forecasting future periods. These non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation between these non-GAAP measures and the most directly comparable GAAP measures is provided later in this press release.

Conference Call Information

Reata’s management will host a conference call on August 8, 2022, at 8:30 am ET. The conference call will be accessible by dialing (844) 200-6205 (toll-free domestic) or (929) 526-1599 (international) using access code 964090. The webcast link is View Source

Second quarter 2022 financial results to be discussed during the call will be included in an earnings press release that will be available on the Company’s website shortly before the call at View Source and will be available for 12 months after the call. The audio recording and webcast of the conference call will be accessible for at least 90 days after the event at View Source.