On May 10, 2021 ImmunoGen Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported financial results for the quarter ended March 31, 2021 (Press release, ImmunoGen, MAY 10, 2021, View Source [SID1234579591]).

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"During the first quarter, we advanced our portfolio of innovative ADCs and accelerated preparations for two potential product launches next year," said Mark Enyedy, ImmunoGen’s President and Chief Executive Officer. "We saw a limited delay in patient enrollment in the pivotal SORAYA trial for our lead program, mirvetuximab soravtansine, which has shifted the anticipated timing of top-line data from the third into the fourth quarter of this year and the projected submission of the BLA into the first quarter of 2022. We have also experienced some COVID-related impact on accrual to our confirmatory MIRASOL trial and now expect the read-out on the primary endpoint to move from the second into the third quarter of 2022. Beyond SORAYA and MIRASOL, we are commencing several studies to move mirvetuximab into earlier lines of ovarian cancer therapy, including an investigator-sponsored trial of mirvetuximab in combination with carboplatin in the neoadjuvant setting that initiated this quarter. We are also supporting a randomized study comparing mirvetuximab combined with carboplatin to standard of care in patients with recurrent platinum-sensitive disease and have submitted a protocol to FDA for a single-arm study of mirvetuximab monotherapy in later-line platinum-sensitive patients, with both studies anticipated to begin enrollment in the second half of this year. Finally, we were pleased to receive notice that mature data from our mirvetuximab plus Avastin doublet cohort in recurrent ovarian cancer, regardless of platinum status, have been selected for an oral presentation at ASCO (Free ASCO Whitepaper) in June."

Enyedy added, "We continued enrollment for our second pivotal program, IMGN632, in patients with frontline and relapsed/refractory BPDCN, with top-line data expected in the first half of 2022. IMGN632 is also in ongoing development in AML, both as a monotherapy and in combinations. Moving to our earlier-stage portfolio, we presented preclinical data at AACR (Free AACR Whitepaper) last month on IMGC936, our first-in-class ADAM9-targeting ADC, demonstrating anti-tumor activity in multiple solid tumor models, and we advanced dose escalation in the Phase 1 study for this program. IND-enabling activities for our next-generation anti-FRα ADC, IMGN151, are on track to submit an application to the FDA by the end of 2021. With pre-commercial activities underway, we look forward to a meaningful year ahead with a number of important milestones across the business as we work towards bringing our first two therapies to market next year."

RECENT PROGRESS

Further enrolled patients in the pivotal SORAYA and confirmatory MIRASOL trials.
Supported initiation of an investigator-sponsored trial of mirvetuximab plus carboplatin in the neoadjuvant setting.
Submitted to the US Food and Drug Administration (FDA) a single-arm study protocol for mirvetuximab monotherapy in later-line platinum-sensitive ovarian cancer patients.
Advanced accrual of the pivotal 801 Phase 1/2 study of IMGN632 in frontline and relapsed/refractory (R/R) blastic plasmacytoid dendritic cell neoplasm (BPDCN) patients.
Continued patient enrollment in the 802 Phase 1b/2 study of IMGN632 in combination with Vidaza (azacitidine) and Venclexta (venetoclax) in R/R and frontline acute myeloid leukemia (AML) patients and as a monotherapy in minimal residual disease positive (MRD+) AML.
Presented preclinical data on IMGC936, our novel ADAM9-targeting ADC in co-development with MacroGenics, in a poster at the virtual American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.
Moved through dose-escalation cohorts in the Phase 1 study of IMGC936 in multiple solid tumor types.
Progressed activities to support an investigational new drug (IND) application for IMGN151.
ANTICIPATED UPCOMING EVENTS

Generate top-line pivotal SORAYA data in the fourth quarter of 2021 and submit the biologics license application (BLA) in the first quarter of 2022 to support potential accelerated approval in 2022.
Complete patient enrollment in MIRASOL and generate top-line data in the third quarter of 2022.
Present mature data from the Phase 1b FORWARD II cohort evaluating mirvetuximab in combination with Avastin (bevacizumab) in recurrent ovarian cancer in an oral presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June.
Initiate a single-arm study of mirvetuximab monotherapy in recurrent platinum-sensitive ovarian cancer in the second half of 2021 to support potential label expansion.
Support the start of a randomized Phase 2 investigator-sponsored study of mirvetuximab plus carboplatin in recurrent platinum-sensitive ovarian cancer in the second half of 2021.
Present initial AML combination data for IMGN632 at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December.
Complete dose escalation in the Phase 1 study evaluating IMGC936, with initial data anticipated in early 2022.
Submit the IND application for IMGN151 by the end of 2021.
FINANCIAL RESULTS

Revenues for the quarter ended March 31, 2021 were $15.7 million, compared with $13.3 million for the quarter ended March 31, 2020, which consisted primarily of non-cash royalty revenues.

Operating expenses for the first quarter of 2021 were $44.6 million, compared with $37.1 million for the same quarter in 2020. The increase was largely driven by research and development expenses, which were $34.4 million in the first quarter of 2021, compared with $27.4 million for the first quarter of 2020. This increase was primarily due to greater clinical trial expenses driven by costs related to the MIRASOL, SORAYA, and IMGC936 studies, greater external manufacturing costs, and greater personnel and temporary staffing costs. General and administrative expenses for the first quarter of 2021 increased to $10.2 million, compared to $8.9 million for the first quarter of 2020, primarily due to increased professional fees and personnel costs, including greater stock-based compensation. Operating expenses for the first quarter of 2020 included a $0.8 million restructuring charge related to retention costs.

Net loss for the first quarter of 2021 was $34.1 million, or $0.17 per basic and diluted share, compared to a net loss of $29.1 million, or $0.17 per basic and diluted share, for the first quarter of 2020. Weighted average shares outstanding increased to 198.8 million for the 2021 period from 166.9 million in the prior year.

ImmunoGen had $283.1 million in cash and cash equivalents as of March 31, 2021, compared with $293.9 million as of December 31, 2020, and had $2.1 million of convertible debt outstanding in each period. Cash used in operations was $44.6 million for the first three months of 2021, compared with cash used in operations of $28.3 million for the same period in 2020. Capital expenditures were $(0.9) million for the first quarter of 2021, compared with net proceeds from the sale of equipment of $1.4 million for the first quarter of 2020.

FINANCIAL GUIDANCE

ImmunoGen’s financial guidance for 2021 remains unchanged:

revenues between $65 million and $75 million;
operating expenses between $200 million and $210 million; and
cash and cash equivalents at December 31, 2021 to be between $140 million and $150 million.
ImmunoGen expects that its current cash will fund operations into the second half of 2022.

CONFERENCE CALL INFORMATION

ImmunoGen will hold a conference call today at 8:00 a.m. ET to discuss these results. To access the live call by phone, dial (877) 621-5803; the conference ID is 9982696. The call may also be accessed through the Investors and Media section of immunogen.com. Following the call, a replay will be available at the same location.

On May 10, 2021 Promega Corporation reported that Serious runners and casual walkers alike are invited to join a month-long Get Your Rear in Gear – Madison run/walk virtual event during May to raise money and awareness for colorectal cancer screening efforts (Press release, Promega, MAY 10, 2021, View Source [SID1234579609]). Colorectal cancer is the nation’s No. 2 cancer killer, but it is up to 95% preventable with proper screening. The number of people being screened has dropped drastically worldwide since the start of the COVID-19 pandemic. The event is aimed to help encourage this important, life-saving health screening.

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"It is imperative that patients are encouraged to get back in with their primary doctor to get screening tests they may have missed," says Dr. Sam Lubner, an oncologist at the University of Wisconsin Carbone Cancer Center. "Without accurate diagnosis as early as possible, all of the advancements we have made in cancer research cannot be brought to bear for patients."

Get Your Rear in Gear – Madison is presented by Promega and Exact Sciences with the support of the Colon Cancer Coalition. This inaugural event is one of nearly 40 held annually across the country planned by local volunteers. Money raised will go to UW Carbone Cancer Center programs aimed at increasing colon cancer screening and early detection.

Registration is open during the entire month of May at www.ColonCancerCoalition.org/Madison. Event participation for colorectal cancer patients and survivors is free. Fundraising by participants is encouraged, but not required.

On May 10, 2021 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688), an innovative commercial-stage biopharmaceutical company, reported financial results for the first quarter of 2021, along with recent product highlights and corporate updates (Press release, Zai Laboratory, MAY 10, 2021, View Source [SID1234579637]).

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"Zai Lab continued to execute well in all aspects of the business during the first quarter," said Dr. Samantha Du, Founder, Chairperson and Chief Executive Officer of Zai Lab. "We entered into several strategic collaborations to further strengthen our gastric and lung cancer disease strongholds; significantly bolstered our autoimmune franchise with an exclusive agreement with argenx for efgartigimod, a pipeline-in-a-product opportunity; advanced numerous clinical programs toward key data readouts; gained approval of QINLOCK by the National Medical Products Administration (NMPA), our third innovative oncology product approval in the last 15 months in China and the first commercial product in what we expect to become a world-class gastric cancer franchise; and generated solid revenue growth, in part from increased volume of ZEJULA driven by its recent inclusion on the National Reimbursement Drug List (NRDL). In addition, we recently received encouraging news on several key assets from our partners. The Biologics License Application (BLA) filing of efgartigimod in generalized myasthenia gravis (gMG) was accepted by the U.S. Food and Drug Administration (FDA). The Phase 3 pivotal LUNAR trial of Tumor Treating Fields in non-small cell lung cancer (NSCLC) was recommended to continue with reduced sample size based on an accelerated interim analysis. Bemarituzumab was granted Breakthrough Therapy Designation by the FDA as first-line treatment for gastric cancer patients who overexpress FGFR2b.

"With the completion of our recent global public offering with gross proceeds of nearly $860 million, we significantly strengthened our capital position. This new capital will allow us to accelerate our growth by entering into additional strategic partnerships, advancing our clinical development pipeline, and scaling our commercial and R&D organizations to drive strong revenue growth and enhance our global pipeline.

"We remain on target to advance all stages of our product pipeline throughout 2021. We continue to expect approval of Nuzyra for community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) by the NMPA. We plan to file margetuximab for Her2-positive breast cancer, Tumor Treating Fields for mesothelioma and ZEJULA for late-line ovarian cancer in China. We are engaging with the NMPA on the regulatory filing strategy for efgartigimod in gMG in China. And we anticipate numerous data readouts, including for Tumor Treating Fields in liver cancer and ovarian cancer, for QINLOCK in second-line GIST, for margetuximab in gastric cancer, for CLN-081 in NSCLC and for TPX-0022 in NSCLC and gastric cancer.

"In our mission to address serious unmet medical needs for patients in China and around the world, we believe that we have built a sustainable platform that we can leverage," Dr. Du concluded. "Our team continues to deliver on our aggressive growth objectives. I believe that the future of Zai Lab has never been brighter."

Recent Product Highlights and Anticipated Milestones

Oncology

ZEJULA (niraparib)

ZEJULA is an oral, once-daily small-molecule poly ADP-ribose polymerase (PARP) 1/2 inhibitor. It is the only PARP inhibitor approved in the United States, the European Union and mainland China (hereinafter, "China") as a monotherapy for patients with advanced ovarian cancer, regardless of their biomarker status.

Anticipated 2021 Zai Milestones

Complete enrollment of the Phase 1b study of ZEJULA in combination with tebotelimab (PD-1 x LAG-3) in gastric cancer.

Announce topline results of the Phase 3 PRIME study of ZEJULA in patients with first-line ovarian cancer in China in the second half.

Submit the supplemental New Drug Application (sNDA) for late-line ovarian cancer treatment in the second half.

Continue to explore additional indications and combination opportunities.
Tumor Treating Fields

Tumor Treating Fields is a cancer therapy that uses electric fields tuned to specific frequencies to disrupt cell division, inhibiting tumor growth and potentially causing cancer cell death.

Recent Product Highlights

In April 2021, Zai Lab partner Novocure announced an update regarding its Phase 3 pivotal LUNAR trial in stage 4 NSCLC following failure on platinum-based chemotherapy. After a review by an independent data monitoring committee (DMC), Novocure was informed by the committee that the pre-specified interim analysis for the LUNAR trial had been accelerated given the length of accrual and the number of events observed. The DMC concluded that it is likely unnecessary and possibly unethical for patients randomized to the control arm to continue accrual to 534 patients with 18 months follow-up. The DMC further recommended a reduced sample size of approximately 276 patients with 12 months follow-up. Novocure has filed an IDE supplement with the FDA and is awaiting the agency’s response.

Zai Lab has initiated the LUNAR trial in Greater China and will help accelerate the development of Tumor Treating Fields for NSCLC and other cancer patients worldwide.
Anticipated 2021 Zai Milestones

Submit a Marketing Authorization Application (MAA) for malignant pleural mesothelioma.

Join the global Phase 3 pivotal PANOVA-3 trial in locally advanced pancreatic cancer, the Phase 3 pivotal INNOVATE-3 trial in recurrent ovarian cancer and the Phase 3 pivotal METIS trial in brain metastases from non-small cell lung cancer.

Complete enrollment of the Phase 2 pilot trial in first-line gastric adenocarcinoma.
Anticipated 2021 Partner Milestones

Receive FDA response to IDE supplement incorporating recommended protocol changes to the Phase 3 pivotal LUNAR trial in NSCLC in the second quarter.

Obtain final data from the Phase 2 HEPANOVA trial in advanced liver cancer in the second quarter.

Complete the interim analysis of the Phase 3 pivotal INNOVATE-3 trial in recurrent ovarian cancer in the second half.
QINLOCK (ripretinib)

QINLOCK is a switch-control tyrosine kinase inhibitor engineered to broadly inhibit KIT- and PDGFRα-mutated kinases. It is the only therapeutic approved in the United States for advanced GIST patients who have received prior treatment with three or more kinase inhibitors in the all-comer setting.

Recent Product Highlight

In March 2021, Zai Lab announced that the NMPA approved its New Drug Application (NDA) for QINLOCK for the treatment of adult patients with advanced gastrointestinal stromal tumors (GIST) who have received prior treatment with three or more kinase inhibitors, including imatinib. This approval is the third innovative oncology product approval Zai Lab has received in the last 15 months in China.
Anticipated 2021 Zai Milestones

Commercial launch of QINLOCK for the treatment of fourth-line GIST in May, 2021.

Obtain regulatory approval in Taiwan in the second half.
Anticipated 2021 Partner Milestones

Obtain topline data from the INTRIGUE Phase 3 study of QINLOCK in patients with second-line GIST in the fourth quarter.
Odronextamab

Odronextamab is a bispecific monoclonal antibody designed to trigger tumor killing by linking and activating a cytotoxic T-cell (binding to CD3) to a lymphoma cell (binding to CD20).

Anticipated 2021 Zai Milestone

Enroll the first patient in Greater China in the global Phase 2 potentially pivotal program, subject to feedback from the FDA.
Anticipated 2021 Partner Milestones

Resume enrollment of the Phase 2 potentially pivotal program in B-cell non-Hodgkin lymphoma (B-NHL) in the second quarter, pending FDA approval of the updated protocol.

Initiate confirmatory OLYMPIA Phase 3 trials in combination with chemotherapy in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), and explore other combination opportunities.

Initiate development of a subcutaneous formulation.
Repotrectinib

Repotrectinib is a next-generation tyrosine kinase inhibitor (TKI) designed to effectively target ROS1 and TRK A/B/C, with the potential to treat TKI-naïve or TKI-pretreated patients.

Anticipated 2021 Zai Milestone

Enroll the first patient in Greater China in the global TRIDENT-1 Phase 2 registrational study in the second quarter.
Anticipated 2021 Partner Milestones

Reach target enrollment of the ongoing TRIDENT-1 study in the ROS1-positive TKI-naïve NSCLC patient cohort. An FDA meeting is anticipated during the first quarter of 2022 to discuss topline blinded independent central review (BICR) results.

Initiate TRIDENT-2, a Phase 1b/2 combination study in KRAS-mutant solid tumors, mid-year.

Provide a clinical data update from the ongoing TRIDENT-1 study in the second half.

Report initial clinical data from the Phase 1/2 CARE study in pediatric and young adult patients in the second half.
MARGENZA (Margetuximab)

MARGENZA is an Fc-optimized monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2).

Anticipated 2021 Zai Milestone

Submit an NDA for pretreated metastatic HER2-positive breast cancer.
Anticipated 2021 Partner Milestones

Obtain initial data from Module A of the MAHOGANY study in the third quarter.

Complete the final overall survival analysis of the SOPHIA study, a randomized, open-label Phase 3 study evaluating margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy in patients with HER2-positive metastatic breast cancer who have previously been treated with HER2-targeted therapies, in the third quarter.
Bemarituzumab

Bemarituzumab is a first-in-class antibody that is being developed in gastric and gastroesophageal junction cancer as a targeted therapy for tumors that overexpress FGFR2b.

Recent Product Highlight

In April 2021, the FDA granted Breakthrough Therapy Designation for bemarituzumab as first-line treatment for patients with fibroblast growth factor receptor 2b (FGFR2b) overexpressing and human epidermal growth factor receptor 2- (HER2-) negative metastatic and locally advanced gastric and gastroesophageal junction adenocarcinoma in combination with modified FOLFOX 6, based on an FDA-approved companion diagnostic assay showing at least 10% of tumor cells overexpressing FGFR2b.
Anticipated 2021 Zai Milestone

Initiate a pivotal Phase 3 trial in gastric cancer.
CLN-081

CLN-081 is an orally available, small-molecule, next-generation, irreversible epidermal growth factor receptor (EGFR) inhibitor designed to selectively target cells expressing mutant EGFR variants, including EGFR exon 20 insertions.

Anticipated 2021 Zai Milestone

Enroll the first patient in Greater China in the global potentially pivotal study in the second half.
Anticipated 2021 Partner Milestone

Provide a clinical data update from the Phase 1/2a global study.
TPX-0022

TPX-0022 is an orally bioavailable, multi-targeted kinase inhibitor with a novel three-dimensional macrocyclic structure that inhibits the MET, CSF1R (colony stimulating factor 1 receptor) and SRC kinases.

Anticipated 2021 Partner Milestones

Provide a clinical data update from the Phase 1 SHIELD-1 study and initiate the Phase 2 portion of the SHIELD-1 study in the second half, pending FDA feedback.

Initiate SHIELD-2, a Phase 1b/2 combination study with an EGFR targeted therapy, in the second half.
Tebotelimab

Tebotelimab is an investigational, first-in-class, bispecific, tetravalent DART molecule targeting PD-1 and LAG-3.

Anticipated 2021 Zai and Partner Milestone

Provide a clinical update, including future development plans.
Retifanlimab

Retifanlimab is an investigational monoclonal antibody that inhibits PD-1.

Recent Product Highlight

In January 2021, our partner Incyte announced that the FDA had accepted for Priority Review its BLA for retifanlimab in patients with pretreated advanced squamous cell anal cancer (SCAC), with a Prescription Drug User Fee Act (PDUFA) date of July 25, 2021.
Autoimmune Diseases

Efgartigimod

Efgartigimod is an antibody fragment designed to reduce disease-causing immunoglobulin G (IgG) antibodies and block the IgG recycling process. Efgartigimod binds to the neonatal Fc receptor (FcRn), which is widely expressed throughout the body and plays a central role in rescuing IgG antibodies from degradation.

Recent Product Highlight

Five Clinical Trial Applications (CTAs) accepted by the NMPA.
Anticipated 2021 Zai Milestones

Discuss with the NMPA a potential accelerated regulatory pathway for efgartigimod in gMG.

Continue to explore and advance additional indications in coordination with argenx.
Receive CTA approvals for additional indications.
Anticipated 2021 Partner Milestones

Potential FDA approval with a PDUFA target action date of December 17, 2021, and global commercial launch of efgartigimod for the treatment of patients with gMG.

Continue enrollment of the registrational ADHERE trial in chronic inflammatory demyelinating polyneuropathy (CIDP).

Initiate clinical trials in fifth and sixth indications.
Infectious Disease

NUZYRA (omadacycline)

NUZYRA is a once-daily oral and intravenous antibiotic for the treatment of adults with CABP and ABSSSI.

Anticipated 2021 Zai Milestone

Potential NMPA approval and commercial launch of NUZYRA for the treatment of CABP and ABSSSI.
Sulbactam-Durlobactam (SUL-DUR)

Sulbactam-Durlobactam is a beta-lactam/beta-lactamase inhibitor combination that provides unique activity against Acinetobacter organisms, including carbapenem-resistant strains.

Anticipated 2021 Zai and Partner Milestone

Complete patient enrollment in the global Phase 3 ATTACK trial, with a top-line data readout anticipated in the second half.
Internal Programs with Global Rights

ZL-2309 (CDC7)

ZL-2309 is an orally active, selective and ATP-competitive cell division cycle 7 (CDC7) kinase inhibitor.

Anticipated 2021 Zai Milestone

Initiate a biomarker-driven POC study in selected tumors.
ZL-1102 (IL-17)

ZL-1102 is a novel human nanobody targeting IL-17 with high affinity and avidity. Unlike other anti-IL-17 products, ZL-1102 is being developed as a topical treatment for chronic plaque psoriasis (CPP).

Anticipated 2021 Zai Milestone

A top-line data readout is anticipated in the second half.
Business Development Updates

In January 2021, Zai Lab announced an exclusive license agreement with argenx for the development and commercialization of efgartigimod in Greater China. Efgartigimod is an antibody fragment designed to reduce disease-causing immunoglobulin G (IgG) antibodies and block the IgG recycling process, with potential application in myasthenia gravis, pemphigus vulgaris, immune thrombocytopenia, chronic inflammatory demyelinating polyneuropathy and several additional indications.

In January 2021, Zai Lab expanded its collaboration with Turning Point Therapeutics with an exclusive license agreement for the development and commercialization of TPX-0022 in Greater China. TPX-0022 is a multi-targeted kinase inhibitor that targets MET, SCF1R and SRC kinases, with potential uses in treating advanced or metastatic solid tumors.
Corporate Updates

In April 2021, Zai Lab announced the closing of a global offering of American depositary shares and ordinary shares, including the full exercise of the greenshoe option, for total gross proceeds to Zai Lab of $857.5 million. This offering was the first ever dual-tranche offering on both NASDAQ and the Hong Kong Stock Exchange.

ZEJULA has been listed in 67 commercial health insurance plans and 52 supplemental insurance plans initiated by provincial or municipal governments since its commercial launch in January 2020 in China. Optune has also been listed in 13 supplemental insurance plans since its commercial launch in June 2020 in China.

On May 7, 2021, Tao Fu took a new role as Chief Strategy Officer of Zai Lab, and transitioned out of his roles as President and Chief Operating Officer and resigned from the Board of Directors of Zai Lab, in order to focus on Zai Lab’s corporate development and other strategic objectives.

Zai Lab continues to expand and hire talented professionals. As of April 15, 2021, Zai Lab employed 1,354 full-time employees, including 514 and 683 employees engaged in R&D and commercial activities, respectively.
First-Quarter 2021 Financial Results

For the three months ended March 31, 2021, net product revenues were $20.1 million, compared to $8.2 million for the same period in 2020. Revenues for the period were comprised of $12.6 million for ZEJULA, compared to $6.3 million for the same period in 2020; and $7.1 million for Optune, compared to $1.9 million for the same period in 2020.

Research and Development (R&D) expenses were $203.9 million for the three months ended March 31, 2021, compared to $33.7 million for the same period in 2020. The increase in R&D expenses was primarily attributable to a $62.3 million upfront payment in Zai Lab equity (fair value of the shares on the closing date of the agreement due to certain restrictions) and a $75 million development cost-sharing payment to argenx; a $25 million upfront payment to Turning Point; expenses related to ongoing and newly initiated late-stage clinical trials; and payroll and payroll-related expenses from increased R&D headcount.

Selling, General and Administrative expenses (SG&A) were $35.8 million for three months ended March 31, 2021, compared to $18.7 million for the same period in 2020. The increase was primarily due to payroll and payroll-related expenses from increased commercial headcount and related costs, as Zai Lab continued to expand its commercial operations in China.

For the three months ended March 31, 2021, Zai Lab reported a net loss of $232.9 million, or a loss per share attributable to common stockholders of $2.64, compared to a net loss of $48.0 million, or a loss per share attributable to common stockholders of $0.66, for the same period in 2020. The increase in the net loss was primarily attributable to payments related to new business development activities with argenx and Turning Point recorded in R&D expenses.
As of March 31, 2021, cash and cash equivalents, short-term investments and restricted cash totaled $1,014.2 million compared to $1,187.5 million as of December 31, 2020. In addition, in April 2021, Zai Lab announced the closing of a global follow-on offering. The expected total proceeds to Zai Lab, including both the American depositary shares offering and the ordinary shares offering, net of underwriting fees and other offering expenses, are approximately $818.1 million.
Conference Call and Webcast Information

Zai Lab will host a live conference call and webcast today, May 10, 2021, at 8:00 a.m. ET. Listeners may access the live webcast by visiting the Company’s website at View Source Participants must register in advance of the conference call. Details are as follows:

Registration Link: View Source

Conference ID: 2374839

All participants must use the link provided above to complete the online registration process in advance of the conference call. Upon registering, each participant will receive a dial-in number, Direct Event passcode and a unique access PIN, which can be used to join the conference call.

A replay will be available shortly after the call and can be accessed by visiting the Company’s website at View Source

On May 10, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a dermatologic diagnostics company providing personalized genomic information to improve treatment decisions, reported its financial results for the first quarter ended March 31, 2021 (Press release, Castle Biosciences, MAY 10, 2021, View Source [SID1234579547]).

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"We are pleased with our strong execution in the first quarter, with revenue increasing by 31% over the first quarter of 2020," said Derek Maetzold, president and chief executive officer of Castle Biosciences. "In-line with our expectations, January and February were impacted, we believe, by COVID-19 and weather interruptions. However, we are encouraged by the positive trends that we are seeing. Specifically, we saw order volume for our DecisionDx-Melanoma test increase by approximately 30% in March 2021, compared to January 2021, with March orders being the highest March since DecisionDx-Melanoma became commercially available. This positive trend continued in April, with April orders exceeding those of March. Additionally, we saw continued positive trends for our recently launched DecisionDx-SCC and DecisionDx DiffDx-Melanoma tests. While there is continued uncertainty related to the impact of COVID-19 with regard to the timing of the return to historical levels of skin cancer diagnoses, we feel confident in providing 2021 revenue guidance of $80-83 million.

"We continue to make progress on our growth initiatives and remain focused on helping physicians answer clinical questions with high unmet need with the personalized, precise results our genomic tests are designed to provide. We believe our recent announcement of signing a definitive agreement to acquire Myriad’s myPath Melanoma laboratory, and the resulting addition of myPath Melanoma test to our skin cancer test services, furthers our position as the leader in dermatologic diagnostics. And we believe this enables us to provide the most comprehensive offerings for patients with skin cancer and difficult-to-diagnose melanocytic lesions. Additionally, our pipeline initiative to develop an innovative test that can predict therapy response and guide treatment selection of systemic therapies in patients diagnosed with moderate to severe psoriasis, atopic dermatitis and related conditions has the potential to expand our reach into non-skin cancer, medical dermatology diseases and is expected to provide enhanced value to our clinical customers and their patients. These tests, along with our other pipeline products, have the potential to increase our estimated U.S. total addressable market to slightly more than $5.5 billion.

"Finally, I am pleased to announce that we completed our commercial team expansion ahead of schedule, with all new outside territories filled, doubling our total dermatology customer facing positions to approximately 60-65. Training is ongoing, and by July 1, we expect our expanded commercial team will be able to utilize our existing, dermatologic sales channels to offer clinicians and their patients four innovative, actionable gene expression profile tests designed to improve patient care."

First Quarter Ended March 31, 2021, Selected Results

Revenues were $22.8 million, a 31% increase compared to $17.4 million during the same period in 2020. Included in revenue for the period were positive revenue adjustments related to tests delivered in prior periods. These positive prior period revenue adjustments for the three months ended March 31, 2021, were $5.3 million, compared to $3.2 million for the same period in 2020. Prior period revenues for the first quarter of 2021 includes favorable adjustments related to settlement of certain groups of receivables from prior years, in addition to other positive prior period revenue adjustments.
Adjusted revenues were $17.5 million, a 22% increase, excluding the effects of revenue adjustments related to tests delivered in prior periods, compared to $14.3 million for the same period in 2020.
Total gene expression profile test reports delivered in the first quarter of 2021 were 5,142, compared to 4,935 in the same period of 2020:
DecisionDx-Melanoma test reports delivered in the first quarter of 2021 were 4,060, compared to 4,574, in the first quarter of 2020.
DecisionDx-SCC test reports delivered in the first quarter of 2021 were 527.
DecisionDx DiffDx-Melanoma test reports delivered in the first quarter of 2021 were 218.
DecisionDx-UM test reports delivered in the first quarter of 2021 were 337, compared to 361 in the first quarter of 2020. Order volume for DecisionDx-UM increased by approximately 58% in March 2021, compared to January 2021.
Gross margin for the three months ended March 31, 2021, was 87%.
Adjusted gross margin for the three months ended March 31, 2021, was 83%.
Operating cash flow was $(3.6) million, compared to $(0.3) million for the same period in 2020.
Adjusted operating cash flow was $(5.5) million, compared to $(0.3) million for the same period in 2020.
Cash and Cash Equivalents

As of March 31, 2021, the Company’s cash and cash equivalents totaled $407 million.

2020 Revenue Guidance

Castle Biosciences anticipates generating $80-83 million in total revenue in 2021.

First Quarter and Recent Business and Clinical Evidence Highlights

On April 27, the Company announced it signed a definitive agreement to acquire all of the equity of Myriad myPath, LLC (Myriad myPath Laboratory), from Myriad Genetics. Myriad myPath Laboratory is a CLIA-certified laboratory in Salt Lake City, where the myPath Melanoma 23-gene expression profile (GEP) test is currently offered. With the acquisition, which is subject to customary closing conditions and is expected to close in late May 2021, Castle expects to make available the most comprehensive molecular testing offering for difficult-to-diagnose melanocytic lesions. See the Company’s news release from April 27, 2021, for more information.
On May 10, the Company announced the launch of its innovative pipeline initiative to develop a genomic test aimed at predicting systemic therapy response in patients with moderate to severe psoriasis, atopic dermatitis and related conditions. See the Company’s news release from earlier today for more information.
In April, at the 10th World Congress of Melanoma, the Company presented data on three of its skin cancer tests, including from an independent validation study demonstrating the i31-GEP artificial intelligence algorithm improves precision of sentinel lymph node positivity prediction in cutaneous melanoma. The poster, titled "Integration of the 31-gene expression profile test with clinicopathologic features (i31-GEP) to assess sentinel lymph node positivity risk in patients with cutaneous melanoma," highlights the i31-GEP validation study data and demonstrates that the algorithm provides a more precise, personalized likelihood of sentinel lymph node positivity. The poster can be accessed here.

Study methods and findings:

The study reviewed the development and validation of the i31-GEP, which deploys a neural network algorithm to integrate the continuous DecisionDx-Melanoma score as well as other histologic and clinical features on a development cohort of 1,398 patients. The i31-GEP algorithm was locked using these 1,398 patients and was then independently validated on an independent, U.S. based cohort of 1,674 patients.
The development phase identified that the DecisionDx-Melanoma score was the most important variable in predicting SLN positivity under both the variable importance assessment function (DecisionDx-Melanoma score = 100, Breslow thickness = 56, Mitotic rate = 25, ulceration = 83 and Age = 0; with 100 being the highest possible value) and log-likelihood value (DecisionDx-Melanoma score = 91.3, Breslow thickness = 53.5, Mitotic rate = 20.7, ulceration = 19.1 and Age = 10.5; with 100 being the highest possible value).
The independent validation phase showed that the i31-GEP provides a highly concordant prediction of SLN positivity rate compared to observed rates (linear regression slope of 0.999, with 1.0 representing complete concordance).
Of patients originally classified with 5-10% SLN positivity risk, i31-GEP reclassified 63% of those patients, whose actual risk of SLN positivity was outside that range in either direction (less than 5% or greater than 10%).
i31-GEP had a high negative predictive value of 98% in patients with T1-T4 tumors.
Information about the additional data presentations can be found here on the Company’s news release from April 16, 2021.

Data from an independent, prospective study was published in the American Journal of Surgery, demonstrating DecisionDx-Melanoma’s utility for prediction of outcomes in patients with cutaneous melanoma. The publication, titled "Utility of a 31-gene expression profile for predicting outcomes in patients with primary cutaneous melanoma referred for sentinel node biopsy," describes a study comparing tumor features, sentinel node biopsy (SLNB) results, and patient outcomes from a prospective database of 383 patients with cutaneous melanoma who both underwent SLNB and had their primary tumor assayed with DecisionDx-Melanoma. The study’s results demonstrated that a Class 2 (high-risk) DecisionDx-Melanoma result was significantly associated with higher rates of SLNB positivity compared to Class 1 (low risk). With respect to risk prognoses, patients who received a Class 2B DecisionDx-Melanoma result and were SLNB-positive experienced the highest recurrence rates (38%), compared to only a 2% recurrence rate for patients who were Class 1A and SLNB-negative. DecisionDx-Melanoma Class 2 results were significantly associated with poorer RFS and DMFS rates compared to Class 1 results, both in the entire cohort of 383 cases and in patients staged as "low risk" (IA-IIA) according to American Joint Committee on Cancer (AJCC) staging criteria. See the Company’s news release from April 14, 2021, for more information.
Publication of prospective, multi-center long-term outcomes data in cutaneous melanoma appeared in the peer-reviewed journal, JCO Precision Oncology, and was titled "Long-term outcomes in a multicenter, prospective cohort evaluating the prognostic 31-gene expression profile for cutaneous melanoma." The study’s key objective was to demonstrate the prognostic value of DecisionDx-Melanoma with long-term follow-up that extends the assessment time period for a previously studied cohort. The study achieved its primary objective and expanded upon prior results to show the ability of the test to accurately identifying recurrence risk of patients with American Joint Committee on Cancer (AJCC) 8th Edition staging system early stage I-IIA disease. See the Company’s news release from April 13, 2021, for more information.
Publication of a cross-sectional study of dermatologists that found its respondents are increasingly incorporating DecisionDx-Melanoma into the management of their patients with melanoma was published in SKIN: The Journal of Cutaneous Medicine and was titled, "Assessment of the 31-Gene Expression Profile Test by Dermatologists: A Cross-Sectional Survey from National Dermatology Conferences." The cross-sectional study was offered to attendees of two national, virtual dermatology conferences during the end of 2020 and beginning of 2021 to assess the professional understanding, opinions and clinical usage of DecisionDx-Melanoma by dermatologists. Participants were asked questions regarding practice demographics, factors considered prior to ordering DecisionDx-Melanoma, their integration of the test’s results into clinical management and their opinions on the usefulness of the test. Participants who use DecisionDx-Melanoma indicated that they use the results to impact follow-up schedules, referrals, surveillance imaging, sentinel lymph node biopsy procedure recommendations and other treatment decisions. These uses largely follow published appropriate-use criteria for the test. Participants responded that patients gain various benefits from DecisionDx-Melanoma test results, including increased knowledge and understanding (70%), personalized treatment options (58%) and eased uncertainty about the future (59%). Even regarding test results indicating the lowest risk of recurrence (i.e., Class 1A), 66% of participants reported potential benefits for ameliorating patients’ anxiety and 46% reported increasing confidence in their management. See the Company’s news release from March 25, 2021, for more information.
In March 2021, the Company announced clinical availability of an artificial intelligence-based integrated DecisionDx-Melanoma test result. The Company validated the integration of clinicopathologic features with the tumor biology insights provided by the DecisionDx-Melanoma test. The integrated test result (ITR) is designed to provide a more precise risk prediction to further improve the clinical actionability by clinicians and their patients in helping to guide cancer management decisions. For more information, see the Company’s news release from March 8, 2021.
In February 2021, the Company presented data on DecisionDx-Melanoma at the 19th Annual South Beach Symposium:
The first poster was entitled, "31-Gene expression profiling improves risk stratification in patients with T1 cutaneous melanoma." Univariate analysis of the study data showed DecisionDx-Melanoma to be a stronger predictor of recurrence-free survival (RFS) than SLN status. Additionally, multivariable analysis showed DecisionDx-Melanoma to be a strong, independent predictor of RFS. With Class 2B RFS status similar to SLN positive status, Class 2B patients warrant follow-up strategies similar to SLN positive patients.
The second DecisionDx-Melanoma poster was entitled, "The clinical and financial impact of the 31-gene expression profile testing on sentinel lymph node biopsy patients selection in patients with T1b cutaneous melanoma." The authors analyzed all clinical DecisionDx-Melanoma tests that were reported from Jan. 3, 2019 through Sept. 4, 2020. The data showed that 75% of eligible patients with T1b tumors had a Class 1A result and could potentially forego sentinel lymph node biopsy (SLNB). The authors estimate that foregoing SLNB in these patients could reduce healthcare expenditures by up to $120 million in SLNB-related costs. For more information, see the Company’s news release from Feb. 4, 2021.
In January 2021, the Company presented data on DecisionDx-Melanoma and DecisionDx DiffDx-Melanoma at the 18th Annual Winter Clinical Dermatology Conference:
The virtual poster for DecisionDx-Melanoma was entitled, "Identifying predictors of sentinel lymph node metastasis in cutaneous melanoma patients using molecular and clinicopathologic high-risk features." For 3,093 patients with T1-T4 cutaneous melanoma, authors used decision tree analysis to determine which molecular and clinicopathologic features best stratify sentinel lymph node (SLN) positivity risk and demonstrated that DecisionDx-Melanoma was the most important feature in distinguishing between high and low SLN-positivity rates (p<0.001).
The virtual poster for DecisionDx DiffDx-Melanoma was entitled, "Performance of a 35-gene expression profile test in suspicious pigmented lesions of the head and neck." The study evaluated DecisionDx DiffDx-Melanoma’s accuracy in classifying pigmented lesions on the head and neck. The data demonstrated that DecisionDx DiffDx-Melanoma has the ability to be an effective tool for refining melanoma diagnoses on the head and neck and therefore improving downstream management decisions, as indicated by its high sensitivity and specificity in the study. For more information, see the Company’s news release from Jan. 20, 2021.
Also in January 2021, the Company presented data at the Maui Derm for Dermatologists 2021 conference:
The virtual poster for DecisionDx-SCC was entitled, "Clinical utility of the 40-gene expression profile (40-GEP) for improved patient management decisions and disease related outcomes when combined with current clinicopathological risk factors for cutaneous squamous cell carcinoma (cSCC): Case Series." Two SCC cases were presented that highlight DecisionDx-SCC’s utility in stratifying risk in SCC. The cases had very similar risk of metastasis at diagnosis as both presented with a history of immunosuppression and had identical staging (T2a per Brigham and Women’s Hospital staging; T1 per American Joint Committee on Cancer staging), but had divergent outcomes:
Case 1 did not recur, despite incomplete resection. This case had a low-risk (Class 1) DecisionDx-SCC result, consistent with the clinical outcome of no clinical progression.
Case 2 developed local recurrence and regional metastasis, and eventually died from SCC, despite clear surgical margins. This case had a highest-risk (Class 2B) DecisionDx-SCC result, consistent with clinical progression. The study authors concluded that incorporating DecisionDx-SCC as a prognostic factor with traditional clinicopathologic risk factors can improve stratification of high-risk SCC patients with at least one risk factor, thereby informing risk-appropriate management strategies.
Conference Call and Webcast Details

Castle Biosciences will hold a conference call on Monday, May 10, 2021, at 4:30 p.m. Eastern time to discuss its first quarter 2021 results and provide a corporate update.

A live webcast of the conference call can be accessed here: View Source or via the webcast link on the Investor Relations page of the Company’s website (www.castlebiosciences.com). Please access the webcast at least 10 minutes before the conference call start time. An archive of the webcast will be available on the Company’s website until June 1, 2021.

To access the live conference call via phone, please dial 877-282-2581 from the United States and Canada, or +1 470-495-9479 internationally, at least 10 minutes prior to the start of the call, using the conference ID 6526639.

There will be a brief Question & Answer session following management commentary.

Use of Non-GAAP Financial Measures (UNAUDITED)

In this release, we use the metrics of Adjusted Revenue, Adjusted Gross Margin and Adjusted Operating Cash Flow, which are non-GAAP financial measures and are not calculated in accordance with generally accepted accounting principles in the United States (GAAP). Adjusted Revenue and Adjusted Gross Margin reflect adjustments to net revenues to exclude changes in variable consideration related to test reports delivered in previous periods. Adjusted Operating Cash Flow excludes the effects of cash activity associated with COVID-19 government relief payments to healthcare providers.

We use Adjusted Revenue, Adjusted Gross Margin and Adjusted Operating Cash Flow internally because we believe these metrics provide useful supplemental information in assessing our revenue and cash flow performance, respectively. We believe Adjusted Revenue and Adjusted Gross Margin are also useful to investors because they provide additional information on current-period performance by removing the effects of revenue adjustments related to tests delivered in previous periods, which we believe may facilitate revenue and gross margin comparisons to historical periods. We believe Adjusted Operating Cash Flow is also useful to investors as a supplement to GAAP measures in the assessment of our cash flow performance by removing the effects of COVID-19 government relief payments, which we believe are not indicative of our ongoing operations. However, these non-GAAP financial measures may be different from non-GAAP financial measures used by other companies, even when the same or similarly titled terms are used to identify such measures, limiting their usefulness for comparative purposes. These non-GAAP financial measures are not meant to be substitutes for net revenues or net cash (used in) provided by operating activities reported in accordance with GAAP and should be considered in conjunction with our financial information presented on GAAP basis. Accordingly, investors should not place undue reliance on non-GAAP financial measures. Reconciliations of these non-GAAP financial measures to the most directly comparable GAAP financial measures are presented in the tables at the end of this press release.

On May 10, 2021 INOVIO (NASDAQ:INO), a biotechnology company focused on rapidly bringing to market precisely designed DNA medicines to treat and protect people from infectious diseases, cancer, and HPV-associated diseases, reported financial results for the quarter ended March 31, 2021 (Press release, Inovio, MAY 10, 2021, View Source [SID1234579574]). INOVIO’s management will host a live conference call and webcast at 4:30 p.m. Eastern Standard Time today to discuss financial results and provide a general business update, covering, among other things: the company’s recently reported Phase 2 segment trial data and plans for a global Phase 3 segment for INO-4800’s INNOVATE Phase 2/3 clinical trial; an overall update on the company’s COVID-19 vaccine developments to address current and future variants of concern (VOC) through its INO-4800 and the pan-COVID INO-4802; and a general update on its DNA medicines platform. The live webcast and replay may be accessed by visiting INOVIO’s website at View Source

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Dr. J. Joseph Kim, President and CEO of INOVIO, said, "As the global community continues to contend with the COVID-19 pandemic, and as we prepare for endemic considerations to support the continued fight against variants, INOVIO remains well-positioned to address the global demand for COVID-19 vaccines. We recognize that there is an opportunity to have a meaningful impact in the fight against COVID-19 outside the U.S. and, are planning for a global Phase 3 trial for INO-4800. INOVIO is also encouraged by the positive data from the Phase 2 segment of our Phase 2/3 trial of INO-4800, which is being conducted in the United States. INO-4800 continues to be safe and well-tolerated and has been observed to support the body’s ability to generate both robust neutralizing antibodies and T cell responses – which we believe to be essential in protecting against current and emerging variants of concern. Equally important, INO-4800 has a favorable thermostability profile and does not require cold or ultra-cold chain transport."

Dr. Kim added, "INOVIO continues to be pleased with the progress across our DNA medicines platform, and our efforts to address not only infectious disease but also cancer and HPV-associated diseases, and we look forward to sharing additional updates on GBM this summer."

INOVIO Key Updates & First Quarter 2021 Highlights

Key Updates

This morning, INOVIO announced positive preliminary immunogenicity and safety data from the Phase 2 segment of INNOVATE (INOVIO INO-4800 Vaccine Trial for Efficacy), its clinical trial evaluating COVID-19 DNA vaccine candidate, INO-4800. The Phase 2 data showed the vaccine to be safe, well-tolerated and immunogenic in all tested age groups. The Phase 2 results from approximately 400 patients helped determine INOVIO’s selection of a 2.0 mg dose for the global Phase 3 segment of the trial.

INOVIO met primary and secondary efficacy endpoints among all evaluable subjects for REVEAL 1 (Randomized Evaluation of VGX-3100 and Electroporation for the treatment of Cervical HSIL) trial. REVEAL 2, the confirmatory Phase 3 trial for VGX-3100, continues to enroll globally across 48 study sites.

INOVIO and QIAGEN extended their partnership in late February with a new master collaboration agreement to include the co-development of a pre-treatment RNA-based biomarker blood test designed to identify prospective patients who are most likely to benefit from the clinical use of VGX-3100.

In February, INOVIO dosed its first patient in a Phase 1b clinical trial for INO-4500, its DNA vaccine candidate for Lassa fever, in Ghana. INO-4500 is the first vaccine candidate for Lassa fever to enter human trials. As part of a 2018 partnership, INOVIO and CEPI are committed to making INO-4500 available for possible emergency use as a stockpile product after successful completion of the Phase 2 trial.

INOVIO First Quarter 2021 Program Updates

DNA Vaccine Candidates

INO-4800: INNOVATE Phase 2/3 Clinical Trial

The Phase 2 segment of INNOVATE was designed to evaluate the safety, tolerability and immunogenicity of INO-4800 in a two-dose regimen (1.0 mg or 2.0 mg) in a three-to-one-randomization to receive either INO-4800 or placebo for each dose to identify optimal dose(s) for two age groups (18-50 years and 51 years and older) for the subsequent Phase 3 efficacy evaluation. The preliminary Phase 2 results showed that INO-4800 was safe, well-tolerated and immunogenic in all tested age groups. The trial was funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, (JPEO-CBRND) in coordination with the Office of the Assistant Secretary of Defense for Health Affairs (OASD(HA)) and the Defense Health Agency. Results from the trial can be found in the paper entitled "Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: A Preliminary Report of a Randomized, Blinded, Placebo-controlled, Phase 2 Clinical Trial in Adults at High Risk of Viral Exposure," has been published as a pre-print in MedRxiv (View Source) prior to peer review.

Findings from the Phase 2 Clinical Trial:

The Phase 2 segment of the trial enrolled approximately 400 participants, 18 years of age or older, at 16 U.S. sites.

Participants received either INO-4800 (1.0 mg or 2.0 mg dose) or placebo at 0 and 4 weeks (randomized 3:3:1:1). Each dose was administered by intradermal injection followed by electroporation using INOVIO’s CELLECTRA, its proprietary smart device.

Safety endpoints included systemic and local administration site reactions through 8 weeks post-dose one (or 4 weeks post-dose 2). Immunology endpoints included antigen-specific binding antibody titers, neutralization titers, and antigen-specific interferon-gamma (IFN-γ) cellular immune responses after two doses of the vaccine.

Vaccine administration was generally safe and well-tolerated. The majority of adverse events (AEs) were Grade 1 and Grade 2 in severity and did not appear to increase in frequency with the second dose. The number of participants experiencing each of the most common AEs did not differ between the two dosing groups.

The geometric mean fold rise of binding and neutralizing antibody levels were statistically significantly greater in the 2.0 mg dose group versus the 1.0 mg dose group.

The T cell immune responses measured by the ELISpot assay were also higher in the 2.0 mg dose group compared to the 1.0 mg dose group.

ClinicalTrials.gov identifier: NCT04642638

Phase 2 results informed INOVIO’s selection of a 2.0 mg dose for the Phase 3 segment of the trial. Given the increasing availability of COVID-19 vaccines authorized for emergency use, in April the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), in coordination with the Office of the Assistant Secretary of Defense for Health Affairs (OASD(HA)) and the Defense Health Agency (DHA), informed INOVIO that it will discontinue funding for the planned Phase 3 segment of the INNOVATE trial, while continuing to fund the completion of the ongoing Phase 2 segment. JPEO informed INOVIO that: "The decision results from the changing environment of COVID-19 with the rapid deployment of vaccines. This decision is not a reflection of the awardee or product, rather a fast-moving environment associated with the former Operation Warp Speed on decisions related to future products." The decision by JPEO does not impact other work that INOVIO does with the U.S. government and is neither a result of the current FDA partial clinical hold nor a reflection of the data generated to date for INO-4800.

Recognizing the need to plan for both pandemic and endemic scenarios, as well as the global demand for safe and effective vaccines that are also stable at room temperature and do not require cold-chain or ultra-cold chain transport, INOVIO also announced in April 2021 that it plans to proceed with a global Phase 3 clinical trial for INO-4800 and is working with funders and partners to achieve this plan. The company plans to initiate the global Phase 3 trial this summer.

INO-4800 and INO-4802: Planning for Existing and Future Variants of Concern

INOVIO continues to evaluate the impact of existing and potential new variants of concern for SARS-CoV-2, the virus that causes COVID-19, as well as assessing boosting capabilities for INO-4800. The company is assessing the impact that new circulating strains of the SARS-CoV-2 virus have on the immune profile elicited by INO-4800.

In April, INOVIO published results from a study showing that INO-4800 provides broad cross-reactive immune responses in humans against variants of concern. The study showed the T cell responses induced by INO-4800 vaccination were fully maintained against the UK, South African and Brazilian variants when compared to the T cell responses to the original Wuhan strain. The neutralization levels of INO-4800 against South African and UK variants were reduced to the levels similar to the previous reports of mRNA or viral vector vaccines. Furthermore, despite recent reports showing a reduction in neutralizing activity against the Brazilian variant by the mRNA or viral vector vaccines, INO-4800 generated robust neutralizing antibodies at levels against the Brazilian variant that were comparable to those observed against the Wuhan strain. Taken together with the data showing the maintenance of T cell activity, the results reported in this study provide a comprehensive overview of cross-reactive cellular and humoral immune responses against SARS-CoV-2 variants for INO-4800 vaccinated individuals, showing the potential of INO-4800 to combat emerging as well as future SARS-CoV-2 variants. The study, entitled "INO-4800 DNA Vaccine Induces T Cell Activity and Neutralizing Antibodies Against Global SARS-CoV-2 Variants," has been submitted for peer review and is available via pre-print in bioRxiv.

In parallel to the late-stage development of INO-4800, the company is also developing a novel, pan-COVID, second-generation vaccine candidate, INO-4802, which is designed to protect against current and potentially future circulating variants. This pan-COVID vaccine could potentially offer boosting capabilities in addition to an initial vaccination regimen with INO-4800 and/or other first-generation vaccines. INOVIO looks forward to sharing additional information on INO-4802 soon.

DNA Immunotherapies: HPV-associated Diseases and Immuno-Oncology

HPV-related Diseases

VGX-3100: Cervical, Vulvar, and Anal HSIL

REVEAL 1 / REVEAL 2 (Cervical HSIL)

In the first quarter, INOVIO announced that it met primary and secondary efficacy endpoints among all evaluable subjects for REVEAL 1 (Randomized Evaluation of VGX-3100 and Electroporation for the treatment of Cervical HSIL), a Phase 3 pivotal trial evaluating VGX-3100 for the treatment of cervical HSIL caused by HPV-16 and/or HPV-18 using the company’s proprietary CELLECTRA 5PSP device. This trial is one of two ongoing pivotal, randomized, double-blind, multi-center, placebo-controlled, Phase 3 trials (REVEAL 1 and REVEAL 2) designed to assess and confirm the safety, tolerability, immunogenicity, and efficacy of VGX-3100.

INOVIO continues to follow subjects in REVEAL 1 for safety and durability of response for 18 months following the last administration and expects to present its findings at a scientific meeting later this year. The company anticipates subject level full unblinding for REVEAL 1 in the second half of 2021, which will facilitate better analysis of individual, patient-level data. Additionally, INOVIO is continuing its partnership with QIAGEN to co-develop an in-vitro diagnostic based on RNA sequencing technology to guide clinical decision-making for the use of VGX-3100 in cervical HSIL. The biomarker blood test could be used to identify prospective VGX-3100 patients who would be most likely to respond to the immunotherapy – an important element of VGX-3100 product and market development. Subject level unblinding for REVEAL 1 will be a key component in enhancing the immune signature of the biomarker, followed by potential confirmatory biomarker data from REVEAL 2.

REVEAL 2 continues to enroll across 48 sites globally. The company continues to assess the impact that the existing pandemic will have on future enrollment in the REVEAL 2 trial. The company believes that it will be in a more suitable position at mid-year to determine if any protocol and/or recruitment adjustments will be necessary.

REVEAL 1 Results

The trial protocol-defined modified intention to treat (mITT) population (N=193) included all subjects with endpoint data. For the primary endpoint of histopathological regression of HSIL combined with virologic clearance of HPV-16 and/or HPV-18 at week 36, the percentage of responders was 23.7% (31/131) in the treatment group, versus 11.3% (7/62) in the placebo group (p=0.022; 12.4% difference in percentage, 95%CI: 0.4,22.5), thus achieving statistical significance. All secondary efficacy endpoints were achieved in the mITT population. These endpoints were: a) regression of cervical HSIL to normal tissue combined with HPV-16 and/or HPV-18 viral clearance, b) regression of cervical HSIL alone, c) regression of cervical HSIL to normal tissue, and d) HPV-16 and/or HPV-18 viral clearance alone. There were no treatment-related serious adverse events and most adverse events were self-resolving and were considered to be mild to moderate, consistent with earlier clinical trials.

Vulvar and Anal HSIL

In January 2021, INOVIO reported positive efficacy results from an open-label Phase 2 trial of VGX-3100 to treat HPV-16 and HPV-18-associated vulvar HSIL. A 25% or more reduction in HPV-16/18-associated vulvar HSIL was observed for 63% of trial participants (12 of 19) treated with VGX-3100 at six months post-treatment. Three out of the 20 participants with histology data (15%) resolved their vulvar HSIL and had no HPV-16/18 virus detectable in the healed area. By comparison, the spontaneous resolution of vulvar HSIL caused by HPV-16/18 is estimated to be 2%. The trial also showed VGX-3100 to be well-tolerated.

The data from the Phase 2 trial of vulvar and anal dysplasia treatments with VGX-3100 were presented at the 2021 ASCCP Virtual Conference. INOVIO continues to evaluate best options for Phase 3 clinical trials for vulvar and anal dysplasia pending further discussions with the FDA.

Immuno-oncology

INO-5401: Newly Diagnosed Glioblastoma Multiforme (GBM)

INOVIO is currently conducting a Phase 1/2 novel combination trial of DNA medicines INO-5401 and INO-9012 in combination with PD-1 inhibitor Libtayo (cemiplimab) – which is being jointly developed by Regeneron and Sanofi – in the treatment of newly diagnosed GBM, the deadliest and most aggressive form of brain cancer. The novel combination of INO-5401 + INO-9012 continues to demonstrate a well-tolerated safety profile when given not only with radiation and chemotherapy, but also with PD-1 blockade by Libtayo.

In late 2020, INOVIO shared encouraging interim OS18 data, which also demonstrated immunogenicity and tolerability in a majority of patients. The company anticipates sharing two-year (24 months) overall survival data, including correlative immunology and tissue data, later this year.

First Quarter 2021 Financial Results

Total revenue was $371,000 for the three months ended March 31, 2021, compared to $1.3 million for the same period in 2020. Total operating expenses were $52.9 million compared to $26.6 million for the same period in 2020.

INOVIO’s net loss for the quarter ended March 31, 2021 was $54.4 million, or $0.27 per basic and diluted share, compared to net loss of $32.5 million, or $0.26 per basic and diluted share, for the quarter ended March 31, 2020.

Operating Expenses

Research and development (R&D) expenses for the three months ended March 31, 2021, were $39.0 million compared to $19.1 million for the same period in 2020. The increase in R&D expenses was primarily related to higher drug manufacturing expenses and outside services related to INO-4800 and other clinical trials, higher employee and contractor compensation, including non-cash stock-based compensation, an increase in engineering services related to our CELLECTRA 3PSP device and higher device inventory expense. These increases were offset by an increase in contra-research and development expense recorded from grant agreements of $8.8 million, among other variances.

General and administrative (G&A) expenses were $13.9 million for the three months ended March 31, 2021, versus $7.4 million for the same period in 2020. The increase in G&A expenses was primarily related to an increase in employee and consultant compensation, including non-cash stock-based compensation and legal expenses, among other variances.

Capital Resources

On January 25, 2021, the company closed an underwritten public offering of 20,355,000 shares of common stock at a price of $8.50 per share. The net proceeds to the company, after deducting the underwriters’ discounts and commissions and other offering expenses, were $162.1 million.

As of March 31, 2021, cash and cash equivalents and short-term investments were $518.6 million compared to $411.6 million as of December 31, 2020. As of March 31, 2021, the company had 209.3 million common shares outstanding and 226.5 million common shares outstanding on a fully diluted basis, after giving effect to the exercise, vesting and conversion, as applicable, of its outstanding options, restricted stock units, convertible preferred stock, and convertible debt.

INOVIO’s balance sheet and statement of operations are provided below. Additional information is included in INOVIO’s quarterly report on Form 10-Q for the quarter ended March 31, 2021, which can be accessed at: View Source

Conference Call / Webcast Information

INOVIO’s management will host a live conference call and webcast at 4:30 p.m. Eastern Time today to discuss INOVIO’s financial results and provide a general business update.

The live webcast and a replay may be accessed by visiting INOVIO’s website at View Source

About INOVIO’s DNA Medicines Platform

INOVIO has 15 DNA medicine clinical programs currently in development focused on HPV-associated diseases, cancer, and infectious diseases, including coronaviruses associated with COVID-19 and MERS, for which programs are being developed with funding support from the U.S. Department of Defense and the Coalition for Epidemic Preparedness Innovations (CEPI). DNA medicines are composed of optimized DNA plasmids, which are small circles of double-stranded DNA that are synthesized or reorganized by a computer sequencing technology and designed to produce a specific immune response in the body.

INOVIO’s DNA medicines deliver optimized plasmids directly into cells intramuscularly or intradermally using INOVIO’s proprietary hand-held smart device called CELLECTRA. The CELLECTRA device uses a brief electrical pulse to reversibly open small pores in the cell to allow the plasmids to enter, overcoming a key limitation of other DNA and other nucleic acid approaches, such as mRNA. Once inside the cell, the DNA plasmids enable the cell to produce the targeted antigen. The antigen is processed naturally in the cell and triggers the desired T cell and antibody-mediated immune responses. Administration with the CELLECTRA device is designed to ensure that the DNA medicine is efficiently delivered directly into the body’s cells, where it can go to work to drive an immune response. INOVIO’s DNA medicines do not interfere with or change in any way an individual’s own DNA. The advantages of INOVIO’s DNA medicine platform are how fast DNA medicines can be designed and manufactured; the stability of the products, which do not require freezing in storage and transport; and the robust immune response, safety profile, and tolerability that have been observed in clinical trials.

With more than 3,000 patients receiving INOVIO investigational DNA medicines in more than 7,000 applications across a range of clinical trials, INOVIO has a strong track record of rapidly generating DNA medicine candidates with potential to meet urgent global health needs.