On August 5, 2020 PTC Therapeutics, Inc. (NASDAQ: PTCT) reported a corporate update and reported financial results for the second quarter ending June 30, 2020 (Press release, PTC Therapeutics, AUG 5, 2020, View Source [SID1234562919]).

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"We are pleased with the progress in our pipeline and the strong commercial performance of our global Duchenne franchise," said Stuart W. Peltz, Ph.D., CEO of PTC Therapeutics. "Our growing revenue stream allows us to continue to invest in the development of treatments leveraging our novel technology platforms. We have a robust pipeline and with more than $1 billion in cash are well positioned to advance multiple differentiated therapies for patients living with rare disorders, not only in the near term, but also for many years to come."

Key Second Quarter and Other Corporate Updates:
•Our Duchenne muscular dystrophy franchise had strong performance in the second quarter. The greater than 30% year-over-year increase in second quarter sales for Emflaza was driven by ongoing improvements in our commercial business. New Duchenne patients continue to be identified in Europe, LATAM and other key markets for Translarna despite the challenges of COVID-19.
•As part of the annual renewal process for Translarna, the European Medicines Agency (EMA) confirmed its risk/benefit profile for the sixth consecutive year. In addition, PTC previously announced that the Committee for Medicinal Products for Human Use (CHMP) of the EMA recommended to remove the statement "efficacy has not been demonstrated in non-ambulatory patients" from the SmPC for Translarna. This label change enables healthcare professionals to use their clinical judgement to make treatment decisions for their patients on Translarna who have lost ambulation and should support reimbursement agencies granting continued access to Translarna.
•In the second quarter, PTC strengthened its pipeline and platforms with the acquisition of a late-stage asset for phenylketonuria (PKU). PTC923 is a clinical-stage investigational therapy for inborn errors of metabolism, including PKU and other diseases associated with defects in the tetrahydrobiopterin (BH4) biochemical pathways diagnosed at birth. PTC is currently conducting nonclinical studies to support the long-term dosing for the planned phase 3 trial in PKU in 2021.
•The U.S. Food and Drug Administration (FDA) PDUFA date for risdiplam is August 24, 2020. In addition, a submission of a marketing authorization application (MAA) to EMA for risdiplam is imminent. The filing of the MAA would trigger a $15 million milestone payment to PTC from Roche. Roche has submitted applications for approval in Brazil, Chile, China, Indonesia, Russia, South Korea and Taiwan.
•PTC recently announced an agreement to monetize a portion of the rights to the risdiplam royalty stream for a $650 million up front payment from Royalty Pharma plc, providing PTC with significant non-dilutive capital. PTC retains nearly 60% of the risdiplam royalty stream up until a $1.3 billion threshold is reached, after which PTC retains 100% of the risdiplam royalty stream. PTC also retains all economics associated with up to approximately $400 million in remaining regulatory and sales milestones.

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•Launch activities for Tegsedi continue to focus on patient finding. Pricing discussions in Brazil are ongoing and are expected to be completed by the end of the year.
•The submission of an application for marketing authorization for Waylivra in patients with familial chylomicronemia syndrome (FCS) has been filed with ANVISA and a decision is expected in 2021. Patient finding and early access programs are ongoing.
•PTC continues to develop manufacturing capabilities for its gene therapy products. It has expanded its collaboration with MassBiologics for the manufacturing of the aromatic L-amino acid decarboxylase deficiency (AADCd) commercial supply. In addition, PTC gained occupancy under its lease of ~220,000 square feet at the former BMS site in Hopewell, NJ. Manufacturing of clinical materials for its gene therapy programs at this site is expected to initiate in 2021.
•PTC recently launched a global internship program, the Talent Pipeline Program (TPP), aimed at providing recent graduates, especially those in minority communities, with real-world experience in the biopharmaceutical industry and related professions, including research, finance, commercial, compliance, quality, legal, information technology, and communications. The TPP will provide approximately 30 interns with a one-year paid program with real-world training experience.

Updates in PTC’s Diverse Product Pipeline
•In its Bio-e platform, PTC expects to initiate potential registrational trials with vatiquinone, formerly known as PTC743, in refractory mitochondrial epilepsy in the third quarter of 2020 and in Friedreich ataxia in the fourth quarter of 2020.
•The first subject has been dosed in the Phase 1 trial for PTC857, PTC’s second compound from the Bio-e platform. Data from the single ascending dose and multiple ascending dose studies is expected by the end of 2020.
•PTC recently initiated a Phase 2/3 clinical trial for PTC299 for COVID-19 called FITE-19. PTC expects Stage 1 to be completed in the second half of 2020 and anticipates reporting top-line results from both stages in the first half of 2021. Multiple sites have been opened in the U.S., Brazil, Spain and Australia with additional countries for Stage 2 expected to initiate in the coming months.
•In the novel splicing platform, the Huntington disease program remains on track for the initiation of first-in-human studies in 2020.
•PTC expects to initiate submission of the biologics license application (BLA) to the U.S. FDA in the second half of 2020 for its AADCd gene therapy program.
•Due to COVID-19 related delays, PTC now expects the final opinion from the CHMP on the MAA for the AADCd program in the first quarter of 2021.
•Given the evolving COVID-19 situation in the U.S., the final study muscle biopsies have not yet been collected from 8 remaining boys in the Translarna (ataluren) dystrophin study. PTC is continuously monitoring the situation to determine when it will be possible to safely obtain the final biopsies and is exploring all potential options in order to have a data read out by the end of 2020. All patients in the study remain on Translarna until they are able to complete the final study visit.

Financial Highlights:
•Total net product revenues were $75.2 million across our commercial portfolio for the second quarter of 2020, compared to total net product revenues of $85.5 million for the second quarter of 2019.
•Translarna net product revenues were $38.6 million for the second quarter of 2020, compared to $57.8 million for the second quarter of 2019. Revenues for the second quarter of 2020 were impacted by the timing of a group purchase order from Brazil, which is the primary driver for the year-over-year decrease, as the second quarter of 2019 included a significant group purchase order from Brazil. Due to the impact of the pandemic, there was an administrative delay by the

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Brazilian Ministry of Health in receiving the centralized Translarna group purchase order. PTC anticipates a group purchase order from Brazil later this year.
•Emflaza net product revenues were $36.2 million for the second quarter of 2020, compared to $27.6 million for the second quarter of 2019. Growth in net product revenues was driven by new patient prescriptions and continued operational improvements and efficiencies in our commercial business.
•Generally accepted accounting principles in the U.S. (GAAP) research and development (R&D) expenses were $176.5 million for the second quarter of 2020, compared to $60.0 million for the second quarter of 2019. The increase in R&D expenses includes one-time charges of $53.6 million related to the acquisition of Censa Pharmaceuticals, and $41.2 million related to the MassBiologics of the University of Massachusetts Medical School agreement for commercial manufacturing of our lead gene therapy program in AADCd.
•Non-GAAP R&D expenses were $168.0 million for the second quarter of 2020, excluding $8.6 million in non-cash, stock-based compensation expense, compared to $54.5 million for the second quarter of 2019, excluding $5.5 million in non-cash, stock-based compensation expense.
•GAAP selling, general and administrative (SG&A) expenses were $53.7 million for the second quarter of 2020, compared to $49.2 million for the second quarter of 2019. The increase reflects continued investment to support our commercial activities including our expanding commercial portfolio.
•Non-GAAP SG&A expenses were $45.3 million for the second quarter of 2020, excluding $8.3 million in non-cash, stock-based compensation expense, compared to $43.8 million for the second quarter of 2019, excluding $5.4 million in non-cash, stock-based compensation expense.
•Change in the fair value of deferred and contingent consideration was $7.7 million for the second quarter of 2020, compared to $5.3 million for the second quarter of 2019. The change in fair value of deferred and contingent consideration is related to the fair valuation of potential future consideration to be paid to former equity holders of Agilis Biotherapeutics, Inc. (Agilis) in connection with PTC’s acquisition of Agilis, which closed in August 2018.
•Settlement of deferred and contingent consideration was $10.6 million for the second quarter of 2020. The settlement of deferred and contingent consideration is related to a loss upon the settlement of the deferred and contingent consideration liabilities as a result of the rights exchange agreement with certain former shareholders of Agilis, whereby such former shareholders exchanged their pro rata share of specific future cash milestone payments in the aggregate amount of $225 million for a mixture of cash and equity of PTC. Under this agreement, which the former shareholders and PTC entered into on April 29, 2020, PTC has paid $36.9 million in cash and issued 2,821,176 shares of common stock in exchange for the cancellation and forfeiture of the participating shareholders’ rights to receive (i) $174.0 million, in the aggregate, of potential milestone payments based on the achievement of certain regulatory milestones and (ii) $37.6 million, in the aggregate, of $40.0 million in development milestone payments that would have been due upon the passing of the second anniversary of the closing of the Merger, regardless of whether the milestones are achieved.
•Net loss was $181.4 million for the second quarter of 2020, compared to net loss of $41.8 million for the second quarter of 2019.
•Cash, cash equivalents and marketable securities were $498.9 million as of June 30, 2020, compared to $686.6 million as of December 31, 2019.
•Shares issued and outstanding as of June 30, 2020 were 67,240,679.

On August 5, 2020 Kezar Life Sciences, Inc. (Nasdaq: KZR), a clinical-stage biotechnology company discovering and developing breakthrough treatments for immune-mediated and oncologic disorders, reported its second quarter 2020 financial results and corporate highlights (Press release, Kezar Life Sciences, AUG 5, 2020, View Source [SID1234562918]).

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"Our excitement continues to build around the novel mechanism of KZR-616 and supports our conviction that targeting master regulators of cellular function – like the immunoproteasome – can benefit patients in need," said John Fowler, Kezar’s Chief Executive Officer. "Our recent fundraising has established a strong balance sheet to allow us to prosecute our robust pipeline."

Noreen Henig, M.D., Kezar’s Chief Medical Officer added, "We are encouraged by the striking early signs of efficacy and the favorable safety and tolerability we’ve seen with KZR-616 and believe in its potential to be a profound treatment option for a wide array of autoimmune diseases. Based on recent events, we plan to adjust our clinical development plans to optimize and expedite the development pathway for KZR-616. In addition, activities related to KZR-261, the first molecule to come forward from our protein secretion inhibition platform, continue as planned for an IND submission in the first quarter of 2021."

Clinical Highlights & Updates

KZR-616 – Selective Immunoproteasome Inhibitor

KZR-616 is currently being evaluated for the treatment of severe autoimmune diseases.

On June 3, 2020, Kezar provided a data update from the Phase 1b portion of the MISSION study. Overall, improvements were seen across seven measures of disease activity in a majority of patients, and two of two patients with lupus nephritis (LN) experienced a greater than 50% reduction in proteinuria, a biomarker of disease severity. A positive safety and tolerability profile was observed with step-up dosing of KZR-616. The Phase 1b dataset builds on the safety and tolerability evaluation performed in 100 healthy subjects from two Phase 1a studies.

Based upon the positive results from the Phase 1b portion of MISSION and acknowledging the recent slowdown in recruitment activities across clinical trials due to the COVID-19 pandemic, Kezar has reviewed and adapted its clinical plans to optimize the development pathway for KZR-616. Kezar will be focusing all development efforts on 60 mg and 45 mg once-weekly subcutaneous dosing of KZR-616. This decision is based on the positive safety and tolerability, pharmacology, and clinical activity results seen to date.

The revised clinical plan for the MISSION Phase 2 trial in patients with active, proliferative lupus nephritis include the following updates:

The Phase 2 protocol has been amended, and the primary endpoint has been changed from safety and tolerability to an efficacy endpoint of renal response measured by 50% or greater reduction in urine protein to creatinine ratio (UPCR) at six months. This study is now open for enrollment under the amended protocol.

The inclusion/exclusion criteria of the study have been expanded to include LN patients with histologic Class III or IV +/- Class V being treated with current standard-of-care. The open-label clinical trial is designed to enroll 20 patients with a single treatment arm evaluating a 60 mg dose (with first dose of 30 mg) of KZR-616 administered subcutaneously once weekly for 24 weeks.

Interim data are expected in late 2021. To allow for responding patients to continue treatment with KZR-616, a 12-month extension study is being planned.

The PRESIDIO Phase 2 trial of KZR-616 in dermatomyositis and polymyositis continues to enroll. A 12-month open-label extension study is being planned and will be available for patients completing the trial.

The MARINA study in patients with autoimmune hemolytic anemia and immune thrombocytopenia has been withdrawn. A combination of COVID-related slowdowns in screening activities and a need to substantially amend the current protocol to reduce high screen failure rates factored into this decision. No new clinical data has informed this decision, and Kezar’s scientific conviction level remains high that KZR-616 could be an important new therapy for patients with these serious diseases. Data from KZR-616 in other studies will inform the optimal strategy for the development of this product candidate in these indications.

KZR-261 – Protein Secretion Program

KZR-261, a first-in-class protein secretion inhibitor, targets the Sec61 translocon and has demonstrated broad anti-tumor activity in preclinical models of both solid and hematologic malignancies. Additional preclinical data further detailing the ability of novel Sec61 inhibitors to exhibit broad anti-cancer activity with minimal toxicity in vitro and in vivo was presented in an e-poster during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (ASCO20) Virtual Scientific Program at the end of May.

An Investigational New Drug application for KZR-261 is planned for submission in the first quarter of 2021. The first-in-human clinical trial will evaluate dose escalation and safety and tolerability in patients with solid tumors.

Business Update

On June 11, 2020, Kezar closed an underwritten public offering with gross proceeds of approximately $46.7 million, before deducting underwriting discounts and commissions and offering expenses. In the public offering, Kezar issued and sold 7,590,909 shares of common

stock at $5.50 per share and pre-funded warrants to purchase 909,091 shares of common stock at $5.499 per share, with an exercise price of $0.001 per share. In July, Kezar issued and sold an additional 427,707 shares of common stock at $5.50 per share, pursuant to the exercise by the underwriters of their option to purchase additional shares, with gross proceeds of approximately $2.4 million.

Financial Results

Cash, cash equivalents and marketable securities totaled $157.5 million as of June 30, 2020, compared to $78.2 million as of December 31, 2019. The increase in cash, cash equivalents and marketable securities was primarily attributable to the net proceeds from the underwritten public offerings in February and June 2020, net of cash used by the Company in operations to advance its clinical stage programs and preclinical research and development.

Research and development expenses for the second quarter of 2020 increased by $0.2 million to $7.1 million, compared to $6.9 million in the second quarter of 2019. This increase was primarily related to advancing the protein secretion preclinical program

General and administrative expenses for the second quarter of 2020 increased by $0.3 million to $2.7 million, compared to $2.4 million in the second quarter of 2019. The increase was primarily due to an increase in personnel expenses, including non-cash stock-based compensation.

Net loss for the second quarter of 2020 was $9.5 million, or $0.22 per basic and diluted common share, compared to a net loss of $8.7 million, or $0.46 per basic and diluted common share, for the second quarter of 2019.

Total shares of common stock outstanding were 45.8 million as of June 30, 2020. Additionally, there were outstanding pre-funded warrants to purchase 3.8 million shares of common stock at an exercise price of $0.001 per share and outstanding options to purchase 4.5 million shares of common stock at a weighted average exercise price of $6.09 per share as of June 30, 2020.

Conference Call and Webcast Information

Kezar will be a hosting a conference call and webcast at 4:30 EDT today. To access the live conference call via phone, dial 877-407-9711 (U.S. toll-free) or 412-902-1014 (toll). No conference ID is required. Additionally, a live webcast of the call will be available under the Events section of the Kezar’s Investor Relations (IR) site at View Source An archived replay of the call will also be available on the company’s IR site for 90 days following the live call.

About KZR-616

KZR-616 is a novel, first-in-class, selective immunoproteasome inhibitor with broad therapeutic potential across multiple autoimmune diseases. Preclinical research demonstrates that selective immunoproteasome inhibition results in a broad anti-inflammatory response in animal models of several autoimmune diseases, while avoiding immunosuppression. Data generated from Phase 1a and 1b trials provide evidence that KZR-616 exhibits a favorable safety and tolerability profile for development in severe, chronic autoimmune diseases. Phase 2 trials are underway in severe autoimmune diseases.

About KZR-261

KZR-261, a novel, first-in-class protein secretion inhibitor, is the first clinical candidate to be nominated from Kezar’s research and discovery efforts targeting protein secretion pathways. KZR-261 is a broad-spectrum anti-tumor agent that acts through direct interaction and inhibition of Sec61 activity. The compound was discovered at Kezar through a robust medicinal chemistry campaign in which several scaffolds were progressed through the company’s proprietary platform evaluating Sec61 modulation. As a result, Kezar has established a broad library of protein secretion inhibitors. KZR-261 has demonstrated several encouraging properties that lead to its potential to be an anti-cancer agent for the treatment of solid and hematologic malignancies. IND-enabling activities are currently underway, and an IND submission in solid tumors is expected to be filed in the first quarter of 2021.

On August 5, 2020 G1 Therapeutics, Inc. (Nasdaq: GTHX), a clinical-stage oncology company, today provided a corporate and financial update for the second quarter ended June 30, 2020 (Press release, G1 Therapeutics, AUG 5, 2020, View Source [SID1234562917]).

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"We made substantial progress on a number of fronts in the first half of 2020, and sharpened our focus on bringing trilaciclib to patients in 2021. By forging four strategic collaborations and securing a flexible credit facility, we have achieved three important objectives: positioning G1 for a strong commercial launch of trilaciclib in the United States, providing global access to our therapies, and securing non-dilutive capital to support the continued development of trilaciclib in additional indications," said Mark Velleca, M.D., Ph.D., Chief Executive Officer. "We are now executing a comprehensive launch strategy for trilaciclib designed to raise awareness of the burden that chemotherapy-induced myelosuppression places on patients and the healthcare system, as well as implementing a robust development plan to evaluate the benefits of trilaciclib in additional tumor types and chemotherapy regimens."

Regulatory, Clinical and Corporate Highlights

NDA for trilaciclib in small cell lung cancer (SCLC) submitted in June 2020. Pending acceptance, the company expects to receive a PDUFA date assignment by the U.S. Food and Drug Administration (FDA) in August 2020. Trilaciclib has been assigned Breakthrough Therapy Designation by the FDA.

Entered into co-promotion agreement with Boehringer Ingelheim for trilaciclib in SCLC in the United States and Puerto Rico. Under the terms of the three-year agreement, G1 and Boehringer Ingelheim will collaborate on the commercialization of trilaciclib for its first potential indication in SCLC. G1 will lead marketing, market access and medical engagement initiatives, with Boehringer Ingelheim leading sales force engagement initiatives. G1 will book revenue and retain development and commercialization rights to trilaciclib (press release here).

Partnered with Simcere to develop and commercialize trilaciclib in Greater China. The company entered into an exclusive agreement with Simcere Pharmaceuticals Group for the development and commercialization of trilaciclib for all indications in Greater China (mainland China, Hong Kong, Macau, and Taiwan). Under the terms of the agreement, G1 received a $14 million upfront payment and is eligible to receive sales-based royalties and up to $156 million in potential milestone payments (press release here). As part of this agreement, the company will collaborate with Simcere on future clinical trials. G1 and Simcere will be responsible for all development and commercialization costs in their respective territories.

I-SPY 2 neoadjuvant breast cancer trial including trilaciclib initiated in 2Q20. Trilaciclib was selected for inclusion in the ongoing Phase 2 I-SPY 2 TRIAL, based on compelling overall survival findings in a Phase 2 triple-negative breast cancer (TNBC) trial (press release here). The I-SPY trial will generate data across a range of breast cancer subtypes that will allow the company to evaluate trilaciclib in combination with several broadly-used chemotherapy classes and an anti-PD-1 immunotherapy.

Rintodestrant and Ibrance combination trial initiated in 2Q20. The company previously announced preliminary safety, tolerability and efficacy data on rintodestrant, its oral selective estrogen receptor degrader (SERD) (press release here) as monotherapy treatment for ER+, HER2- breast cancer. Based on these findings, G1 initiated an additional arm of its ongoing Phase 1/2a trial to evaluate the combination regimen of rintodestrant and the CDK4/6 inhibitor Ibrance (palbociclib). Palbociclib is being provided by Pfizer Inc. under a non-exclusive clinical supply agreement.

Out-licensed global development and commercialization rights to lerociclib. The company entered into separate, exclusive agreements with EQRx (rights for U.S., Europe, Japan, and all markets outside Asia-Pacific) and Genor Biopharma (rights for Asia-Pacific, excluding Japan) for the development and commercialization of lerociclib in all indications. Combined, these agreements provided $26 million in upfront payments to G1, along with sales-based royalties and up to $330 million in potential milestone payments (see press releases on EQRx agreement and Genor agreement). EQRx and Genor are responsible for all costs related to the development and commercialization of lerociclib in their respective territories.

Out-licensed global development and commercialization rights to preclinical CDK2 inhibitor compounds. The company entered into an exclusive license agreement with ARC Therapeutics for global development and commercialization rights to its preclinical CDK2 inhibitor compounds. Under the terms of the agreement, G1 received an upfront payment and equity in ARC with an aggregate value of approximately $2.1 million. The company is also entitled to receive an additional milestone payment and sales-based royalties, and has right of first negotiation to re-acquire these assets.

Secured flexible credit financing for up to $100 million. The company announced it had entered into a debt financing agreement for up to $100 million with Hercules Capital, Inc. G1 has accessed $20 million to support the development and commercialization of trilaciclib (press release here).

Second Quarter 2020 Financial Highlights and 2020 Guidance

Cash Position: Cash and cash equivalents totaled $234.3 million as of June 30, 2020, compared to $269.2 million as of December 31, 2019.

License Revenue: License revenues were $2.1 million for the second quarter of 2020, related to the license of CDK2 inhibitor compounds to ARC Therapeutics.

Operating Expenses: Operating expenses were $33.0 million for the second quarter of 2020, compared to $32.6 million for the second quarter of 2019. GAAP operating expenses include stock-based compensation expense of $4.4 million for the second quarter of 2020, compared to $3.7 million for the second quarter of 2019.

Research and Development Expenses: Research and development (R&D) expenses for the second quarter of 2020 were $18.5 million, compared to $23.5 million for the second quarter of 2019. The decrease in R&D expenses was primarily due to a decrease in clinical program costs of $3.4 million and regulatory filing reimbursement received during the second quarter of 2020 for $3.0 million, offset by an increase in costs for manufacturing active pharmaceutical ingredients.

General and Administrative Expenses: General and administrative (G&A) expenses for the second quarter of 2020 were $14.4 million, compared to $9.1 million for the second quarter of 2019. The increase in G&A expenses was largely due to an increase in compensation due to additional headcount, increase in pre-commercialization activities, increase in medical affairs costs, and an increase in professional fees and other administrative costs necessary to support our operations.

Net Loss: G1 reported a net loss of $31.2 million for the second quarter of 2020, compared to $30.7 million for the second quarter of 2019.

2020 Guidance: The company is increasing its previous financial guidance and expects to end 2020 with $185-$200 million in cash and cash equivalents, up from previous guidance of $110-$130 million. This guidance includes receipt of upfront payments from recent agreements, but does not include consideration of potential additional proceeds from partnerships, collaboration activities, and/or other sources of capital.

Key Anticipated 2020 Milestones

NDA acceptance/PDUFA date assignment for trilaciclib in SCLC in August 2020.

Initiate Phase 3 clinical trial of trilaciclib in colorectal cancer in 4Q20.

Presentation of Phase 2 data of trilaciclib in triple-negative breast cancer in 4Q20.

Presentation of additional rintodestrant monotherapy data in 4Q20.

Webcast and Conference Call

The management team will host a webcast and conference call at 5:00 p.m. ET today to provide a corporate and financial update for the second quarter 2020 ended June 30, 2020. The live call may be accessed by dialing 866-763-6020 (domestic) or 210-874-7713 (international) and entering the conference code: 4648036. A live and archived webcast will be available on the Events & Presentations page of the company’s website: www.g1therapeutics.com. The webcast will be archived on the same page for 90 days following the event.

On August 5, 2020 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a pioneer in T-cell immunotherapy, leveraging its novel allogeneic EBV T-cell platform to develop transformative therapies for patients with severe diseases including solid tumors, hematologic cancers and autoimmune disease, reported financial results for the second quarter ended June 30, 2020 and recent business highlights (Press release, Atara Biotherapeutics, AUG 5, 2020, View Source [SID1234562916]).

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"I am proud of the continued tremendous progress made by Atara’s team in delivering on our strategic priorities and on our mission to bring transformative therapies to patients with severe diseases," said Pascal Touchon, President and Chief Executive Officer of Atara. "We remain on track to initiate a BLA submission for tab-cel for patients with EBV+ PTLD by the end of 2020, despite the COVID-19 outbreak. During the quarter we also reported positive ATA188 clinical data in progressive multiple sclerosis at EAN, successfully completed a follow-on financing, made key executive and board hires, and progressed our CAR T programs closer to the clinic."

Recent Highlights and Anticipated Upcoming Milestones

Tab-cel (tabelecleucel)

Post-transplant lymphoproliferative disease (PTLD)

Atara remains on track to initiate a biologics license application (BLA) submission for patients with EBV+ PTLD by the end of 2020.

The Company continues to advance development of tab-cel in Phase 3 for patients with EBV+ PTLD, for which the Company has obtained Breakthrough Therapy Designation (BTD) in the United States (U.S.) and PRIority MEdicines (PRIME) designation in the European Union (EU).

The Company plans to conduct an interim analysis of the tab-cel Phase 3 study in the third quarter of 2020 and then discuss the totality of tab-cel data with the U.S. Food and Drug Administration (FDA) in a pre-BLA meeting prior to initiating the BLA submission.

Atara is in active discussions with the Pediatric Committee (PDCO) of the European Medicines Agency (EMA) regarding a Pediatric Investigation Plan (PIP). Following discussion with the PRIME team and after EMA approval of the PIP, Atara plans to submit an EU marketing authorization application (MAA) for patients with EBV+ PTLD in 2021.

In the U.S., Europe and Australia, more than 40 clinical study sites are available for enrollment, with new sites in Spain, Austria and Belgium.

Given the severity of previously treated PTLD, time sensitivity for treatment and promising clinical results to date with tab-cel, Atara continues to provide tab-cel to patients in need under its expanded access protocol (EAP) and single patient use (SPU) programs.

Tab-cel Potential Additional Indications

Atara remains on track to initiate enrollment in the second half of 2020 in a tab-cel Phase 2 multi-cohort study, enriching the evidence base with the goal of expanding the potential label in PTLD and closely related diseases.

Atara will focus on extending further into IA-LPDs (immunodeficiency-associated lymphoproliferative diseases) as the next step in the tab-cel potential label expansion given the commonality of their EBV-driven mechanism of disease in immunocompromised patients, high unmet medical need and positive clinical data to date with tab-cel.

The multi-cohort study will evaluate both treatment-naïve and previously treated patients in six patient populations, including within IA-LPDs, two cohorts addressing front-line EBV+ PTLD patients with significant unmet need as well as two cohorts addressing EBV+ LPDs arising out of primary or acquired immune deficiencies including AID-LPD and PID-LPD (EBV+ acquired immunodeficiency-associated lymphoproliferative disease and EBV+ primary immunodeficiency-associated lymphoproliferative disease).

Altogether these populations represent an additional few thousand patients with addressable EBV-driven diseases in the U.S. alone.

Previously reported clinical data from ASH (Free ASH Whitepaper) (2018) and ESMO (Free ESMO Whitepaper) (2018) suggest that tab-cel may provide benefit for patients with other EBV-driven diseases. Atara will publish tab-cel efficacy and safety data in AID-LPD and PID-LPD in an e-poster accepted at ESMO (Free ESMO Whitepaper) 2020.

Based on a strategic prioritization to expand tab-cel business potential through the significant opportunity in IA-LPDs, the Company will now focus its tab-cel efforts on the initiation of the multi-cohort Phase 2 study and the planned BLA initiation in EBV+ PTLD.

The Company’s Phase 1b study of tab-cel in combination with anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in patients with platinum-resistant or recurrent EBV-associated nasopharyngeal carcinoma (NPC) achieved its safety endpoints and stable disease in a subset of patients. These data will be presented at an appropriate forum in the future.
At this time, Atara will not initiate the Phase 2 portion of the NPC study in combination with pembrolizumab but will generate additional translational data in NPC to further inform the Company’s strategy for this patient population.

ATA188 for Progressive Multiple Sclerosis (MS)

Atara’s Phase 1a clinical study of off-the-shelf, allogeneic ATA188 in patients with progressive forms of MS is ongoing across clinical sites in the U.S. and Australia.

Safety and sustained disability improvement (SDI) 12-month data for cohorts 1-3, and six-month data for cohort 4, were presented at the 2020 European Academy of Neurology Virtual Congress (EAN) held in May 2020.

All patients in cohorts 1-3 showing SDI at six months maintained improvement at 12 months and there was a higher proportion of patients showing SDI with increasing dose. SDI is defined as clinically significant improvement in Expanded Disability Status Scale (EDSS) or timed 25-foot walk (T25FW) observed at two consecutive time points. While these data will need to be confirmed in a double-blind, placebo-controlled, randomized study, they indicate the potential for the first treatment option in progressive MS to halt or reverse the progression of disease. These results align with the body of evidence supporting the important role of EBV-infected B cells in the chronic autoimmune pathology of MS.

ATA188 was well-tolerated in patients with progressive forms of MS and no dose-limiting toxicities and no fatal adverse events (AEs) have been reported. ATA188 treatment showed no clinically meaningful effect on cytokine levels and no dose-related safety trends were identified. Rhinorrhea (runny nose) is the only treatment-related event that occurred in more than one subject.

Atara expects to present 12-month clinical results for cohort 4 at an appropriate forum in the second half of 2020.

Atara is re-treating patients in the open-label extension (OLE) of the Phase 1a study and expects to present preliminary OLE data, at an appropriate forum in the second half of 2020.

Based on the promising data presented at EAN, the cohort 3 dose from the Phase 1a study was selected for the double-blind, randomized placebo-controlled study evaluating the efficacy and safety of ATA188 in patients with progressive forms of MS. The study design allows for addition of the cohort 4 dose, if desired, based on the 12-month data for cohort 4 that will be available in the third quarter of 2020.

The study enrolled its first patient in June 2020. In addition to measuring change in disability measures compared to baseline, especially sustained disability improvement over time, the study will also include multiple measures of patients’ function as well as various biomarkers.

CAR T Programs

ATA2271/ATA3271 (Solid tumors)

Atara’s next generation CAR T immunotherapy programs include autologous ATA2271 targeting mesothelin–a tumor antigen expressed on a number of solid tumors including mesothelioma, ovarian cancer, pancreatic cancer, non-small cell lung cancer, and other tumors over-expressing mesothelin.

ATA2271 is designed to improve efficacy, persistence, and durability of response versus CD28/CD3z-based CARs in using a novel 1XX CAR co-stimulatory signaling domain and cell intrinsic checkpoint inhibition technology with a PD-1 dominant negative receptor (DNR).

Data from IND-enabling studies for ATA2271 were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II in June 2020. These data support the first application of the combination of 1XX CAR co-stimulatory domain and cell intrinsic checkpoint inhibition technology with a PD-1 DNR, that are associated with less cell exhaustion, improvements in functional persistence, serial cell killing, and in vivo efficacy which was maintained through multiple tumor re-challenges when compared with first-generation CD28/CD3z-based mesothelin CAR.

ATA2271 collaborators at Memorial Sloan Kettering Cancer Center (MSK) recently submitted an Investigational New Drug (IND) application to the FDA for patients with advanced mesothelioma.

Atara is also developing and has initiated IND-enabling studies for ATA3271, an off-the-shelf, allogeneic CAR T immunotherapy targeting mesothelin using its novel combination of 1XX CAR co-stimulatory signaling domain and cell intrinsic checkpoint inhibition technology with a PD-1 DNR through its EBV T-cell platform.

ATA3219 (B-cell)

Atara is developing ATA3219, an off-the-shelf, allogeneic CD19 CAR T immunotherapy targeting B-cell malignancies as a potential best-in-class therapy using the next-generation 1XX CAR co-stimulatory domain and EBV T-cell platform. Atara intends to leverage the differentiation of 1XX and allogeneic EBV T cell to address remaining unmet need despite currently approved autologous CD19 CAR T and other allogeneic CD19 cell therapies in development.

Findings from an academic, off-the-shelf, allogeneic CD19 CAR T clinical study using an allogeneic EBV T-cell construct and CD28/CD3z co-stimulatory domain for patients with relapsed/refractory B-cell malignancies provided initial clinical proof-of-principle that an EBV T-cell platform has the potential to generate off-the-shelf, allogeneic CAR T immunotherapies with high response rates, durable responses, and low risk of toxicity. These results were presented in February at the 2020 Transplantation and Cellular Therapy Meetings.

The Company has initiated IND-enabling studies for ATA3219 and anticipates filing an IND in 2021.

Operations

Atara continues to advance key elements of its off-the-shelf, allogeneic T-cell immunotherapy platform.

Atara is completing the manufacturing process validation activities for tab-cel while building inventory according to its commercial product supply strategy.

Atara continues to scale its EBV T-cell manufacturing platform to improve product yields from a single donor leukapheresis. The Company has generated data confirming the use of stirred-tank perfusion bioreactors to improve yield and cell growth productivity.

These data confirm that ATA188 can be manufactured in stirred-tank perfusion bioreactors, with the potential to produce up to 40,000 doses per donor leukapheresis.

Atara’s scale-up technology is a key enabler to deliver biologic-like cost of goods manufactured and will be leveraged across its portfolio, including the Company’s CAR T programs.

Despite the challenges of the COVID-19 environment, Atara continues to consistently deliver product from inventory to clinical sites on time.

Executive and Board Appointments

Two scientific leaders in the field of cell and gene therapy recently joined Atara in its mission to leverage its novel, allogeneic EBV T-cell platform to develop transformative therapies for patients with severe diseases:

Jakob Dupont, M.D. was named Executive Vice President, Global Head of R&D. He possesses deep and diverse expertise from cell therapy research to oncology clinical development and global regulatory approvals. Dr. Dupont joined Atara from Gossamer Bio where he served as Chief Medical Officer, and held previous roles at Genentech/Roche and OncoMed. At Memorial Sloan Kettering Cancer Center (MSK), Dr. Dupont served on faculty and worked in the laboratories of Richard O’Reilly, M.D., the scientific inventor of tab-cel, and Michel Sadelain, M.D., Ph.D, Atara’s collaborator on multiple next generation CAR T programs.

Maria Grazia Roncarolo, M.D. was appointed to the Board of Directors. Dr. Roncarolo holds several professorships and director roles at Stanford University, and in 2014 established the Stanford Center for Definitive and Curative Medicine. The center is dedicated to the development of innovative stem cell and gene therapies for patients with currently incurable diseases. Dr. Roncarolo is one of the world’s leading experts in immunology and T cells and has a record of translating scientific discoveries in cell and gene therapy into novel treatments.

Second Quarter 2020 Financial Results

Cash, cash equivalents and short-term investments as of June 30, 2020 totaled $347.7 million, as compared to $214.6 million as of March 31, 2020.

June 30, 2020 cash balance of $347.7 million included aggregate net proceeds of $189.3 million from the sale of 14,958,039 shares of common stock and pre-funded warrants to purchase 2,866,961 shares of common stock in May and June of 2020 in an underwritten public offering, including the full exercise of the option to purchase additional shares by the underwriters.

Atara believes that its cash, cash equivalents and short-term investments as of June 30, 2020 are sufficient to fund planned operations into 2022.

Net cash used in operating activities was $56.6 million for the second quarter of 2020, as compared to $54.6 million for the same period in 2019.

The number of outstanding shares of common stock and pre-funded common stock warrants as of June 30, 2020 was 74,307,894 shares and warrants to purchase 5,755,487 shares, respectively.

Atara reported net losses of $77.5 million, or $1.14 per share, for the second quarter of 2020, as compared to $74.3 million, or $1.60 per share, for the same period in 2019.

Total operating expenses include non-cash expenses of $15.9 million for the second quarter 2020, as compared to $16.9 million for the same period in 2019.

Research and development expenses were $61.6 million for the second quarter of 2020, as compared to $52.3 million for the same period in 2019. The increase in the 2020 period was due to costs associated with the Company’s continuing expansion of research and development activities, including:

Clinical study, manufacturing and process performance qualification activities related to tab-cel.

Higher employee-related costs from increased headcount.

Research and development expenses include $8.5 million of non-cash stock-based compensation expenses for the second quarter of 2020, as compared to $6.7 million for the same period in 2019.

General and administrative expenses were $16.4 million for the second quarter of 2020, as compared to $23.3 million for the same period in 2019. The decrease in the 2020 period was primarily due to a decrease in outside services costs and non-cash stock-based compensation expenses.

General and administrative expenses include $5.4 million of non-cash stock-based compensation expenses for the second quarter of 2020, as compared to $8.5 million for the same period in 2019.

On August 5, 2020 Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) reported financial results for its fiscal third quarter ended June 30, 2020 (Press release, Arrowhead Research Corporation, AUG 5, 2020, View Source [SID1234562915]). The company is hosting a conference call at 4:30 p.m. EDT to discuss results.

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Conference Call and Webcast Details

Investors may access a live audio webcast on the Company’s website at View Source For analysts that wish to participate in the conference call, please dial 855-215-6159 or 315-625-6887 and provide Conference ID 6856804.

A replay of the webcast will be available on the company’s website approximately two hours after the conclusion of the call and will remain available for 90 days. An audio replay will also be available approximately two hours after the conclusion of the call and will be available for 3 days. To access the audio replay, dial 855-859-2056 or 404-537-3406 and provide Conference ID 6856804.

Selected Recent Events

Earned a $20 million milestone payment from Amgen following the administration of the first dose of AMG 890, formerly referred to as ARO-LPA, in a Phase 2 clinical study

Hosted a key opinion leader webinar on ARO-ENaC, the company’s investigational RNAi therapeutic being developed as a treatment for patients with cystic fibrosis

Completed dosing in healthy volunteer cohorts in AROHSD1001, a Phase 1/2 clinical study of ARO-HSD, the company’s investigational RNAi therapeutic being developed as

a treatment for patients with alcohol related and nonalcohol related liver diseases, such as nonalcoholic steatohepatitis

Completed dosing of the first sequential cohort and collected the first 6-month repeat biopsy in the AROAAT2002 study, a pilot open-label, multi-dose, Phase 2 study to assess changes in a novel histological activity scale in response to ARO-AAT over time in patients with alpha-1 antitrypsin deficiency associated liver disease

Completed planned enrollment and dosing of 93 subjects in AROANG1001, a Phase 1/2 clinical study of ARO-ANG3, the company’s investigational RNAi therapeutic being developed for the treatment of mixed dyslipidemia

Completed planned enrollment and dosing of 80 subjects in AROAPOC31001, a Phase 1/2 clinical study of ARO-APOC3, the company’s investigational RNAi therapeutic being developed for the treatment of hypertriglyceridemia, and expanded the study to include up 112 subjects