On August 8, 2022 Lipocine Inc. (NASDAQ: LPCN), a biopharmaceutical company focused on developing innovative products to treat metabolic and central nervous system ("CNS") disorders, reported financial results for the second quarter ended June 30, 2022 and provided a corporate update (Press release, Lipocine, AUG 8, 2022, View Source [SID1234617762]).

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Second Quarter Highlights

In June, Lipocine’s commercial partner Halozyme launched TLANDO (testosterone undecanoate), an oral treatment indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone (primary or hypogonadotropic hypogonadism).
In July 2022, Lipocine held an End of Phase 2 meeting with the FDA for LPCN 1144 in NASH. The FDA recommends Lipocine conduct a phase 2 dose ranging study to identify the optimal dose prior to conducting a pivotal study. The FDA agreed to the proposed unique testosterone ester, testosterone dodecanoate, for future clinical studies.
LPCN 1111: Technology transfer for our once-a-day testosterone product candidate was completed. Scale up and manufacturing of registration batches is ongoing.
Lipocine continues to enroll subjects in a Phase 2 proof-of-concept study to evaluate the therapeutic potential of LPCN 1148 for the management of cirrhosis, with enrollment in the study expected to be complete in the second half of 2022.
A type C meeting was held with the FDA to discuss the clinical development path of LPCN 1154, our candidate for postpartum depression ("PPD"). Based on feedback from the meeting, the company plans to initiate a multi-dose proof-of-concept study of LPCN 1154 in the second half of 2022.
The FDA accepted the company’s Investigational New Drug Application ("IND") for its neuroactive steroid ("NAS") candidate, LPCN 2101, as a potential treatment for adults with epilepsy. Lipocine plans to initiate a Phase 2 photosensitive epilepsy ("PSE") study to evaluate the safety, tolerability, and efficacy of oral LPCN 2101 in women with epilepsy of childbearing age.
We continue to explore partnering LPCN 1111, LPCN 1144, LPCN 1107 and TLANDO ex-US to third parties.

Second Quarter Ended June 30, 2022 Financial Results

Lipocine reported a net loss of $2.6 million, or ($0.04) per diluted share for the quarter ended June 30, 2022, compared with a net loss of $6.8 million, or ($0.08) per diluted share, in the quarter ended June 30, 2021.

Revenues in the quarter ended June 30, 2022 were $0.5 million related to a non-refundable cash fee received from Antares for consideration of a 90-day extension to exercise its option to license LPCN 1111. Antares’ option to license TLANDO XR expired on June 30, 2022 and was not exercised. There was no revenue in the comparable quarter of 2021.

Research and development expenses were $2.9 million for the quarter ended June 30, 2022, compared with $1.5 million for the quarter ended June 30, 2021. The increase in research and development expenses for the quarter ended June 30, 2022, was a result of an increase in contract research organization expense related to the Phase 2 POC study in male cirrhotic subjects with LPCN 1148, an increase in costs related to LPCN 1154 clinical studies, increases in personnel expenses, and an increase in costs related to LPCN 1111 scale up and LPCN 1107 expenses. These increases were offset by a decrease in contract research organization expenses and outside consulting costs related to the completion of the LiFT Phase 2 clinical study in NASH subjects in 2021, a decrease in costs associated with TLANDO, as well as a decrease in other R&D expenses.

General and administrative expenses were $1.1 million for the quarter ended June 30, 2022, compared with $1.5 million for the quarter ended June 30, 2021. The decrease in general and administrative expenses was primarily due to decreases in legal expenses and personnel costs. These decreases were offset by an increase in professional fees, an increase related to proxy solicitation and proxy distribution services, an increase in corporate insurance expenses, and an increase in other general and administrative expenses.

As of June 30, 2022, the company had $37.4 million of unrestricted cash, cash equivalents and marketable investment securities, compared to $46.6 million at December 31, 2021.

Six Months Ended June 30, 2022 Financial Results

Lipocine reported a net loss of $6.1 million, or ($0.07) per diluted share, for the six months ended June 30, 2022, compared with a net loss of $10.2 million, or ($0.12) per diluted share, in the six months ended June 30, 2021.

Revenues in the six months ended June 30, 2022 were $0.5 million related to a non-refundable cash fee received from Antares for consideration of a 90-day extension to exercise its option to license LPCN 1111, as described above. There was no revenue in the comparable period of 2021.

Research and development expenses for the six months ended June 30, 2022, were $4.8 million compared to $3.0 million for the comparable period in 2021. The increase in research and development expenses was due to an increase in contract research organization expense related to the Phase 2 POC study in male cirrhotic subjects with LPCN 1148, an increase in costs related to LPCN 1154 clinical studies, an increase related to LPCN 1111 scale up activities, a food effect study in LPCN 1107, and an increase in personnel expenses and other research and development costs. These increases were offset by a decrease in contract research organization expense and outside consulting costs related to the completion of our LPCN 1144 LiFT Phase 2 clinical study in NASH subjects in 2021, and a decrease in costs associated with TLANDO.

General and administrative expenses for the six months ended June 30, 2022 were $2.4 million compared to $3.1 million for the comparable period in 2021. The decrease in general and administrative expenses was primarily due to decreases in legal expenses, personnel costs, and other general and administrative expenses. These decreases were offset by an increase in professional fees, an increase related to proxy solicitation and proxy distribution services, an increase in various other consulting fees, and an increase in corporate insurance expenses.

On August 8, 2022 Pulmatrix, Inc. (NASDAQ: PULM), a clinical-stage biopharmaceutical company developing innovative inhaled therapies to address serious disease using its patented iSPERSE technology, reported second quarter financial results for 2022 and provided a corporate update related to its development programs (Press release, Pulmatrix, AUG 8, 2022, View Source [SID1234617761]).

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Ted Raad, Chief Executive Officer of Pulmatrix commented, "Our focus this quarter has been on advancing both PUR3100 and Pulmazole towards important data catalysts. We initiated patient dosing for PUR3100, our orally inhaled dihydroergotamine (DHE), in a Phase 1 study with data anticipated in Q4 2022. In addition to safety and tolerability, the study will evaluate the pharmacokinetics of PUR3100 and intravenous dihydroergotamine (DHE). This will allow us to better understand the potential efficacy and tolerability profile of PUR3100." Mr. Raad continued, "We also commenced study start-up activities for the Pulmazole Phase 2b study and remain on track to initiate patient dosing in Q1 2023. Pulmazole has the potential to be the first approved therapy for treatment of Allergic Bronchopulmonary Aspergillosis (ABPA) in patients with Asthma."

Second Quarter 2022 and Recent Program Highlights

Pulmazole (PUR1900)

Pulmatrix initiated study start-up activities for the Phase 2b efficacy study of Pulmazole, which will include a 16-week dosing regimen and potential registration endpoints that would potentially support a registrational trial.
PUR3100

On July 12, 2022, Pulmatrix announced the dosing of the first five subjects in a Phase 1 trial. To date, the trial has enrolled 23 of 24 patients and top-line data is anticipated in Q4 2022.
PUR1800

Pulmatrix is analyzing data from the completed Phase 1b clinical study of PUR1800 for future publication and conducting further modeling to inform the Phase 2 study design.
Second Quarter 2022 Financial Results

Revenue was $1.3 million for the second quarter ended June 30, 2022, compared to $2.2 million for the same period in 2021, a decrease of $0.9 million. The decrease in revenue was due to no revenues recorded for this period for the PUR1800 program offset by a $1.0 million increase in revenues recorded this period over same period in 2021 on the Cipla Agreement for Pulmazole (PUR1900).

For the three months ended June 30, 2022, research and development expenses were $4.3 million compared to $4.5 million for the same period in 2021, a decrease of $0.2 million. The decrease was primarily due to decreased spending of $0.9 million in preclinical and clinical costs related to the PUR 1800 program and $0.5 million in preclinical and manufacturing costs related to the PUR 3100 program, partially offset by increased spending of $0.6 million in clinical and manufacturing costs related to the Pulmazole program, $0.5 million in employment costs and $0.1 million in facility costs.

General and administrative expenses were unchanged at $1.6 million for the three months ended June 30, 2022 compared to the same period in 2021.

Total cash and cash equivalents balance as of June 30, 2022 was $42.9 million. Pulmatrix expects its existing cash and cash equivalents as of June 30, 2022 will enable it to fund operating expenses and capital expenditure into Q2 2024.

On February 28, Pulmatrix completed a reverse stock-split at a ratio of 1-for-20 (the "Reverse Split") which reduced the number of outstanding shares of the Company’s common stock from approximately 65.9 million shares to 3.3 million shares.

On August 8, 2022 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage gene editing company developing ARCUS-based ex vivo allogeneic CAR T and in vivo gene editing therapies, reported financial results for the second quarter ended June 30, 2022 and provided a business update (Press release, Precision Biosciences, AUG 8, 2022, View Source [SID1234617742]).

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"This past quarter, we have executed on many important aspects of our business. From manufacturing optimization to clinical trial progress to business development and operational advancements, we are making strides towards delivering on the potential of ARCUS genome editing for drug development and adding significant cash to our balance sheet. Most exciting this past quarter, we entered into a collaboration agreement with Novartis to develop a potential one-time treatment option for hemoglobinopathies including sickle cell disease and beta thalassemia using ARCUS for gene insertion. We are very excited about expanding ARCUS into potential indications that require more complex edits, such as gene insertion," said Michael Amoroso, Chief Executive Officer at Precision BioSciences.

"For our CAR T programs, Q2 2022 was also an exciting time for us to share encouraging new interim clinical data for our lead PBCAR0191 program. We believe the latest update validated the signal of high response rates to PBCAR0191 observed among CAR T relapsed patients we reported at the 2021 American Society for Hematology (ASH) (Free ASH Whitepaper) meeting, further supporting our potential path forward in this patient population. We have recently released optimized batches of our PBCAR19B clinical trial material and look forward to commencing dosing in the next cohort of patients this quarter. In addition, we dosed PBCAR269A in combination with nirogacestat at Dose Level (DL) 3. We expect to provide additional updates across our CAR T portfolio by the end of the year," concluded Michael Amoroso.

Recent Developments and Upcoming Milestones:

Ex Vivo Allogeneic CAR T Portfolio:

PBCAR0191: PBCAR0191, azercabtagene zapreleucel (azer-cel), is Precision’s lead investigational anti-CD19 allogeneic CAR T candidate in a Phase 1/2a clinical trial of adult subjects with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL). In June 2022, Precision provided new interim data as of May 31, 2022, including high and durable clinical response rates among subjects who received a median of five prior lines of therapy. Evaluable subjects in the latest cohort of the study had the following results:

100% Overall Response Rate (ORR) and 73% Complete Response (CR) rate

50% durable response rate greater than six months

No Grade 3 or greater cytokine release syndrome (CRS) was observed in either dosing cohort. One Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) was recorded in each cohort that rapidly resolved to Grade 1 within 24 to 48 hours. Two Grade 5 events associated with late occurring encephalopathy suspected to be related to fludarabine-associated neurotoxicity occurred. There was no evidence of graft versus host disease.

In the second half of 2022, Precision plans to continue dosing subjects with optimized PBCAR0191 CAR T cells in this relapsed patient population while further reducing its lymphodepletion dose to standard levels.

PBCAR19B: PBCAR19B is Precision’s second generation, anti-CD19 targeting allogeneic CAR T candidate designed to evade immune rejection by host T cell and natural killer (NK) cells with a single-gene edit to knock-down beta-2 microglobulin and insert an HLA-E transgene. Manufacturing optimization for PBCAR19B was implemented in the first quarter of 2022. New clinical trial material has been released, and the company plans to commence dosing in the next cohort, DL 2 (flat dose of 540 million cells), in the third quarter of 2022.

PBCAR269A: PBCAR269A is Precision’s investigational allogeneic CAR T cell candidate targeting B-cell maturation antigen (BCMA) for R/R multiple myeloma. Precision is evaluating PBCAR269A in a Phase 1/2a study in combination with nirogacestat, a gamma secretase inhibitor (GSI) developed by SpringWorks Therapeutics. Precision has completed DL2 (2.0 × 106 cells/kg) of PBCAR269A plus GSI and is initiating the next cohort at DL3 (flat dose of 480 ×106 cells) to further evaluate efficacy. To date, peak expansion rates observed at DL2 plus the GSI have been equivalent to DL4 (960 × 106 cells flat dose) monotherapy with no dose limiting toxicities observed.

Precision expects to provide the next update on its clinical ex vivo allogeneic CAR T programs toward year-end 2022.

In Vivo Gene Editing Portfolio:

Novartis In Vivo Gene Editing Collaboration: In June 2022, Precision announced it had entered into an exclusive worldwide in vivo gene editing research and development collaboration and license agreement with Novartis. As part of the agreement, Precision will develop a single, custom ARCUS nuclease designed to insert, in vivo, a therapeutic transgene at a "safe harbor" location in the genome as a potential one-time transformative treatment option for diseases including certain hemoglobinopathies such as sickle cell disease and beta thalassemia. Precision will conduct in vitro characterization, with Novartis then assuming responsibility for all subsequent research, development, manufacturing and commercialization activities.

In addition to a $25 million equity investment from Novartis in Precision’s common stock at $2.01 per share received in June 2022, Precision received an upfront cash payment of $50 million on July 12, 2022 and is eligible to receive up to an aggregate amount of approximately $1.4 billion in additional payments for future milestones. Precision is also eligible to receive certain research funding and tiered royalties ranging from the mid-single digits to low-double digits on product sales, should Novartis successfully commercialize a therapy from the collaboration.

Lilly In Vivo Gene Editing Programs: Precision continues its in vivo gene editing collaboration with Lilly and is applying ARCUS nucleases for three initial targets, including Duchenne muscular dystrophy in muscle, a central nervous system directed target and a liver directed target.

PBGENE-PH1: Precision has initiated IND-enabling activities for its PBGENE-PH1 candidate designed to knock out the HAO1 gene as a potential one-time treatment for primary hyperoxaluria type 1 (PH1). In the first quarter of 2022, the Company initiated a non-human primate (NHP) study for PBGENE-PH1 delivered by LNP and is targeting an IND or CTA submission in 2023, subject to evaluation of data from the ongoing preclinical NHP study. Preclinical data for Precision’s PBGENE-PH1 was presented at the 2022 American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting and demonstrated a robust knockdown of the HAO1 protein in non-human primates following a single administration of an ARCUS nuclease via AAV.

PBGENE-HBV: Precision’s gene editing program for chronic Hepatitis B applies ARCUS to knock out persistent covalently closed circular DNA (cccDNA) and inactivate integrated hepatitis B genomes, potentially achieving durable HBV S-antigen (HBsAg) loss and reducing viral persistence. Preclinical data from this program was presented during the Gene Editing in Cancer and Complex Diseases oral session at the ASGCT (Free ASGCT Whitepaper) Annual Meeting and within the same month published online in Molecular Therapy in May 2022. As reported, ARCUS efficiently targeted and degraded hepatitis B virus (HBV) cccDNA by 85% and reduced expression of HBsAg by 77% in HBV-infected primary human hepatocytes (PHH). Importantly, the optimized specificity of the ARCUS nuclease completely prevented detectable chromosomal translocations in the PHH model. PBGENE-HBV candidate is in pre-clinical development and Precision is targeting an IND/CTA submission in 2024 following completion of pre-clinical and IND enabling studies.

PBGENE-PCSK9: In 2021, Precision initiated a collaboration with iECURE, pursuant to which iECURE is expected to advance Precision’s PBGENE-PCSK9 candidate through preclinical activities as well as a Phase 1 study in familial hypercholesterolemia. As of this date, IND enabling activities for PBGENE-PCSK9 have not been completed. We are in discussions with iECURE and will provide an update on the program when more information is available.

Quarter Ended June 30, 2022 Financial Results:

Cash and Cash Equivalents: As of June 30, 2022, Precision had approximately $184.1 million in cash and cash equivalents, including receipts of $25.0 million from Novartis’ equity investment in the Company and proceeds from the June 2022 underwritten offering of the Company’s common stock, described below. The Company expects that existing cash and cash equivalents, including the cash payment of $50.0 million received from Novartis on July 12, 2022, expected operational receipts, and available credit will be sufficient to fund its operating expenses and capital expenditure requirements to the end of 2024.

In June 2022, Precision announced the closing of an underwritten offering of 35,971,224 shares of its common stock at an offering price of $1.39 per share, for total net proceeds of approximately $46.7 million, after deducting underwriting discounts and commissions and offering expenses payable by the Company.

Revenues: Total revenues for the quarter ended June 30, 2022 were $3.8 million, as compared to $68.8 million for the same period in 2021. The decrease of $65.0 million in revenue during the quarter ended June 30, 2022 was primarily the result of the absence of $62.5 million in revenue recognized under the Servier Agreement in April 2021 subsequent to full satisfaction of the performance obligation, a $1.5 million decrease in revenue recognized under the Lilly Agreement, and a $0.9 million decrease in revenue recognized from an agriculture partnering collaboration.

Research and Development Expenses: Research and development expenses were $22.9 million for the quarter ended June 30, 2022, as compared to $37.2 million for the same period in 2021. The decrease of $14.3 million was primarily due to a decrease of $11.3 million related to the Servier Program Purchase Agreement, a decrease of $2.1 million in external development costs associated with our allogeneic CAR T product candidates, a decrease of $1.3 million in employee-related costs due to reduced headcount, and a decrease of $1.7 million in clinical manufacturing organization and research costs related to our preclinical studies. These decreases were partially offset by a $1.5 million increase in sublicensing royalty payable to Duke on the Novartis upfront payment.

General and Administrative Expenses: General and administrative expenses were $10.5 million for the quarter ended June 30, 2022, as compared to $9.9 million for the same period in 2021. The increase of $0.6 million was primarily due to costs required to meet our growing infrastructure needs, including consulting fees and employee-related costs associated with increased share-based compensation expense.

Net Loss: Net loss was $31.0 million, or $(0.46) per share (basic and diluted), for the quarter ended June 30, 2022, as compared to net income of $21.7 million, or $0.38 per share (basic) and $0.36 per share (diluted), for the same period in 2021.

Corporate:

Executive Leadership: In May 2022, Juli Blanche was appointed Chief People Officer and a member of the senior leadership team. Ms. Blanche joined Precision from Bristol-Myers Squibb where she was Senior Vice President and HR Business Partner, Global Commercialization. She brings over 25 years of strategic business partnership and enterprise leadership experience in the pharmaceutical and financial services industries.

Board of Directors: In May 2022, Melinda Brown was appointed as a Director on Precision’s Board of Directors and Chair of the Board’s Audit Committee. Ms. Brown is a financial expert with proven experience leading accounting, finance and enterprise risk management teams in large, public companies, including Tapestry, Inc. and PepsiCo, Inc.

Together, Ms. Blanche and Ms. Brown provide substantial executive leadership that will be paramount for Precision as the company embarks upon the next phase of its life cycle.

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]).

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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: HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM: HCM, HKEX: 13) and AstraZeneca PLC ("AstraZeneca") (LON/STO/Nasdaq: AZN) reported that preliminary results from the SAVANNAH Phase II trial showed that TAGRISSO (osimertinib) plus savolitinib demonstrated an objective response rate ("ORR") of 49% (95% confidence interval ["CI"], 39-59%) in patients with epidermal growth factor receptor-mutated ("EGFRm") non-small cell lung cancer ("NSCLC") with high levels of mesenchymal epithelial transition ("MET") overexpression and/or amplification, defined as IHC90+ and/or FISH10+, whose disease progressed on treatment with TAGRISSO (Press release, Hutchison China MediTech, AUG 8, 2022, View Source [SID1234617739]).

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The highest ORR was observed in patients with high levels of MET who were not treated with prior chemotherapy (52% [95% CI, 41-63%]). In patients whose tumors did not show high levels of MET, the ORR was 9% (95% CI, 4-18%). These results are being shared at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (WCLC), taking place on August 6-9, 2022 in Vienna, Austria.

Savolitinib, marketed in China under the brand name ORPATHYS, is an oral, potent and highly selective MET tyrosine kinase inhibitor ("TKI") being jointly developed and commercialized by AstraZeneca and HUTCHMED.

While EGFR-targeted therapy can provide a durable survival benefit to patients with EGFRm NSCLC, most will eventually develop resistance to their treatment, with MET being the most common resistance biomarker.1 Among patients screened for enrolment in SAVANNAH, all of whom experienced disease progression on TAGRISSO, 62% had tumors with MET overexpression and/or amplification, and more than one-third (34%) met the defined high MET level cut-off.

Myung-Ju Ahn, MD, PhD, Professor of Hemato-Oncology at the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, and Principal Investigator in the SAVANNAH Phase II trial, said: "Acquired resistance to targeted therapy and disease progression are difficult realities for most patients with EGFR-mutated NSCLC. These preliminary SAVANNAH results potentially support a novel approach for identifying patients with MET overexpression and/or amplification who are most likely to benefit from a MET-directed therapy, like savolitinib. They also suggest that with the right biomarker testing strategy, MET may be a more prevalent target among resistant patients than previously understood, supporting further investigation of the osimertinib plus savolitinib regimen."

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca said: "The current standard of care for patients with EGFR-mutated lung cancer who progress on targeted treatment is chemotherapy. The results from SAVANNAH suggest savolitinib added to TAGRISSO at the time of disease progression could possibly provide these biomarker-selected patients with a potentially less toxic, more effective treatment option. We look forward to better understanding the potential of the TAGRISSO plus savolitinib regimen in this trial and in the SAFFRON Phase III trial."

Weiguo Su, Chief Executive Officer and Chief Scientific Officer, HUTCHMED, said: "It is encouraging to see the savolitinib and TAGRISSO combination regimen progress into a global Phase III study, SAFFRON, with a well-supported patient selection strategy that could benefit more patients than previously recognized. The preliminary results of the SAVANNAH study also affirm the role of molecular testing prior to initiating subsequent treatment for NSCLC patients who experience disease progression on an EGFR-targeted therapy. We are aligned in pursuing a selective, patient-centric approach in development efforts for savolitinib in this setting."

In this analysis, patients’ MET overexpression and/or amplification levels were determined by two tests: immunohistochemistry ("IHC"), which detects if cancer cells have a particular protein or marker on their surface, and fluorescence in situ hybridization ("FISH"), which detects a specific DNA sequence from cancer cells. All patients in this analysis (n=193) had at least IHC50+ and/or FISH5+, and were treated with savolitinib 300mg once daily added to TAGRISSO 80mg once daily following disease progression on TAGRISSO alone.

The safety profile of TAGRISSO plus savolitinib was consistent with the known profiles of the combination and each treatment alone. No new safety signals were identified. Less than half (45%) of patients in this analysis experienced Grade 3 or higher adverse events ("AEs"), with those most frequently reported including pulmonary embolism, dyspnea, decreased neutrophil count and pneumonia. AEs attributable to savolitinib and leading to discontinuation occurred in 13% of patients.

The global SAFFRON Phase III trial will further assess the TAGRISSO plus savolitinib combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following TAGRISSO. Patients are being prospectively selected using the high MET level cut-off identified in SAVANNAH.

About NSCLC and MET aberrations
Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.2 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.3 The majority of NSCLC patients (approximately 75%) are diagnosed with advanced disease and approximately 10-15% of NSCLC patients in the U.S. and Europe and 30-40% of patients in Asia have EGFRm NSCLC.4,5,6,7

MET is a tyrosine kinase receptor that has an essential role in normal cell development.8 MET overexpression and/or amplification can lead to tumor growth and the metastatic progression of cancer cells, and is the primary mechanism of acquired resistance to EGFR TKIs for metastatic EGFR-mutated NSCLC. 8,9 The prevalence of MET depends on the sample type, detection method and assay cut-off used.10

About SAVANNAH
SAVANNAH is an ongoing global, randomized, single-arm Phase II trial studying the efficacy of savolitinib added to TAGRISSO in patients with EGFRm, locally advanced or metastatic NSCLC with MET overexpression and/or amplification who progressed following treatment with TAGRISSO. Patients were treated with savolitinib 300 or 600 mg once-daily (QD) or 300 mg twice-daily, in combination with oral osimertinib 80 mg QD.

The trial has enrolled 294 patients to date in more than 80 centers globally, including centers in the U.S., Canada, Europe, South America and Asia. The primary endpoint is ORR. Key secondary endpoints include PFS, DoR and safety.

About TAGRISSO
TAGRISSO (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. TAGRISSO (40mg and 80mg once-daily oral tablets) has been used to treat approximately 575,000 patients across indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFRm NSCLC.

In Phase III trials, TAGRISSO is being investigated in the neoadjuvant resectable setting (NeoADAURA), in the Stage IA2-IA3 adjuvant resectable setting (ADAURA2), in the Stage III locally advanced unresectable setting following chemoradiation therapy (LAURA), and in combination with chemotherapy in the advanced setting (FLAURA2). AstraZeneca is also researching ways to address tumor mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test TAGRISSO given concomitantly with savolitinib, an oral, potent and highly selective MET TKI, as well as other potential new medicines.

About Savolitinib
Savolitinib is an oral, potent and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.

Savolitinib is marketed in China under the brand name ORPATHYS for the treatment of patients with NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy. It is currently under clinical development for multiple tumor types, including lung, kidney and gastric cancers, as a single treatment and in combination with other medicines.

About AstraZeneca and HUTCHMED collaboration
In 2011, AstraZeneca and HUTCHMED entered a global licensing and collaboration agreement to jointly develop and commercialize savolitinib. Joint development of savolitinib in China is led by HUTCHMED, while AstraZeneca leads development outside of China. HUTCHMED is responsible for the marketing authorization, manufacturing and supply of savolitinib in China. AstraZeneca is responsible for the commercialization of savolitinib in China and worldwide. Sales of savolitinib are recognized by AstraZeneca.

About AstraZeneca in lung cancer
AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and assessing innovative approaches, the Company aims to match medicines to the patients who can benefit most.

The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations including TAGRISSO (osimertinib) and IRESSA (gefitinib); IMFINZI (durvalumab) and tremelimumab; ENHERTU (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; ORPATHYS (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.

AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.

About AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.