On November 8, 2019 EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany in the US and Canada, and Pfizer Inc. (NYSE: PFE) reported topline results of the Phase III JAVELIN Gastric 100 study evaluating avelumab as first-line maintenance therapy following induction chemotherapy in patients with unresectable, locally advanced or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) cancer versus continuation of chemotherapy or best supportive care (Press release, Pfizer, NOV 8, 2019, View Source [SID1234550752]). While the study showed clinical activity for avelumab in this setting, it did not meet the primary endpoints of superior overall survival compared with the standard of care in the overall intent-to-treat population (n=499; HR: 0.91; 95% CI: 0.74, 1.11) or the PD-L1–positive population (n=54; HR: 1.13; 95% CI: 0.57, 2.23).

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"Advanced gastric cancer is a hard-to-treat tumor, and there is a key unmet need for additional treatments. Additionally, it is rarely immunogenic, and to date no immune checkpoint inhibitor has demonstrated superiority to the current standard of care with chemotherapy," said Prof. Dr. Markus Möhler, Head of GI Oncology, Senior Physician Gastroenterology & Endosonography, Johannes-Gutenberg University, Mainz, Germany and coordinating investigator. "As we have yet to define the ideal strategy for incorporating immunotherapy in the continuum of care, the results of JAVELIN Gastric 100 will provide essential information in advancing our understanding and potential treatment options of this challenging disease."

No new safety signals were observed, and the safety profile for avelumab in this trial was consistent with that observed in the overall JAVELIN clinical development program. A detailed analysis of the Phase III JAVELIN Gastric 100 study is being conducted to better understand the results, and findings will be shared with the scientific community.

About JAVELIN Gastric 100
JAVELIN Gastric 100 (NCT02625610) is a Phase III, multicenter, randomized, open-label trial investigating maintenance therapy with avelumab in patients with HER2-negative advanced (unresectable, locally advanced or metastatic) adenocarcinoma of the stomach or of the gastroesophageal junction (GEJ) who have not yet received chemotherapy for the treatment of metastatic or locally advanced disease, in an overall population unselected for PD-L1 expression. A total of 805 patients were enrolled to receive induction (initial) chemotherapy with oxaliplatin and either 5-fluorouracil (5-FU) or capecitabine for 12 weeks. Of these, 499 patients whose disease had not progressed at the end of the 12 weeks of chemotherapy treatment were randomly assigned to receive either avelumab as a maintenance treatment or continuation of the same chemotherapy regimen until disease progression. Patients unfit for further chemotherapy received best supportive care. The primary endpoints are overall survival in all randomized patients or in the PD-L1+ population (≥1%).

About Gastric Cancer
Globally, gastric cancer is the third most common cause of cancer death.1 The standard first-line option for patients with HER2-negative disease is chemotherapy,2 yet patients with advanced disease can experience resistance, leading to a poor prognosis.3 Over the past decade, there have been limited advancements in treatment,4 and the median overall survival for patients at the advanced stage is less than one year.5 In recognition of the significant need, the Merck KGaA, Darmstadt, Germany-Pfizer alliance initiated a Phase III trial to assess a novel first-line maintenance approach in advanced gastric cancer, to understand the potential of checkpoint inhibitor treatment following confirmed response or stabilization of disease on induction chemotherapy.

About the JAVELIN Clinical Development Program
The clinical development program for BAVENCIO, known as JAVELIN, involves more than 10,000 patients evaluated across more than 15 different tumor types. In addition to gastric/gastroesophageal junction cancer, these tumor types include head and neck cancer, Merkel cell carcinoma, non-small cell lung cancer, renal cell and urothelial carcinoma.

About BAVENCIO (avelumab)
BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.6-8 In November 2014, Merck KGaA, Darmstadt, Germany and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.

BAVENCIO Approved Indications
BAVENCIO (avelumab) in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

In the US, the FDA granted accelerated approval for BAVENCIO for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Avelumab is currently approved for patients with MCC in 50 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.

BAVENCIO Important Safety Information from the US FDA-Approved Label
BAVENCIO can cause immune-mediated pneumonitis, including fatal cases. Monitor patients for signs and symptoms of pneumonitis, and evaluate suspected cases with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold BAVENCIO for moderate (Grade 2) and permanently discontinue for severe (Grade 3), life-threatening (Grade 4), or recurrent moderate (Grade 2) pneumonitis. Pneumonitis occurred in 1.2% of patients, including one (0.1%) patient with Grade 5, one (0.1%) with Grade 4, and five (0.3%) with Grade 3.

BAVENCIO can cause hepatotoxicity and immune-mediated hepatitis, including fatal cases. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater hepatitis. Withhold BAVENCIO for moderate (Grade 2) immune-mediated hepatitis until resolution and permanently discontinue for severe (Grade 3) or life-threatening (Grade 4) immune-mediated hepatitis. Immune-mediated hepatitis occurred with BAVENCIO as a single agent in 0.9% of patients, including two (0.1%) patients with Grade 5, and 11 (0.6%) with Grade 3.

BAVENCIO in combination with axitinib can cause hepatotoxicity with higher than expected frequencies of Grade 3 and 4 alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation. Consider more frequent monitoring of liver enzymes as compared to when the drugs are used as monotherapy. Withhold BAVENCIO and axitinib for moderate (Grade 2) hepatotoxicity and permanently discontinue the combination for severe or life-threatening (Grade 3 or 4) hepatotoxicity. Administer corticosteroids as needed. In patients treated with BAVENCIO in combination with axitinib, Grades 3 and 4 increased ALT and AST occurred in 9% and 7% of patients, respectively, and immune-mediated hepatitis occurred in 7% of patients, including 4.9% with Grade 3 or 4.

BAVENCIO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold BAVENCIO until resolution for moderate or severe (Grade 2 or 3) colitis until resolution. Permanently discontinue for life-threatening (Grade 4) or recurrent (Grade 3) colitis upon reinitiation of BAVENCIO. Immune-mediated colitis occurred in 1.5% of patients, including seven (0.4%) with Grade 3.

BAVENCIO can cause immune-mediated endocrinopathies, including adrenal insufficiency, thyroid disorders, and type 1 diabetes mellitus.

Monitor patients for signs and symptoms of adrenal insufficiency during and after treatment, and administer corticosteroids as appropriate. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency. Adrenal insufficiency was reported in 0.5% of patients, including one (0.1%) with Grade 3.

Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation. Manage hypothyroidism with hormone replacement therapy and hyperthyroidism with medical management. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) thyroid disorders. Thyroid disorders, including hypothyroidism, hyperthyroidism, and thyroiditis, were reported in 6% of patients, including three (0.2%) with Grade 3.

Type 1 diabetes mellitus including diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Withhold BAVENCIO and administer antihyperglycemics or insulin in patients with severe or life-threatening (Grade ≥3) hyperglycemia, and resume treatment when metabolic control is achieved. Type 1 diabetes mellitus without an alternative etiology occurred in 0.1% of patients, including two cases of Grade 3 hyperglycemia.

BAVENCIO can cause immune-mediated nephritis and renal dysfunction. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater nephritis. Withhold BAVENCIO for moderate (Grade 2) or severe (Grade 3) nephritis until resolution to Grade 1 or lower. Permanently discontinue BAVENCIO for life-threatening (Grade 4) nephritis. Immune-mediated nephritis occurred in 0.1% of patients.

BAVENCIO can result in other severe and fatal immune-mediated adverse reactions involving any organ system during treatment or after treatment discontinuation. For suspected immune-mediated adverse reactions, evaluate to confirm or rule out an immune-mediated adverse reaction and to exclude other causes. Depending on the severity of the adverse reaction, withhold or permanently discontinue BAVENCIO, administer high-dose corticosteroids, and initiate hormone replacement therapy, if appropriate. Resume BAVENCIO when the immune-mediated adverse reaction remains at Grade 1 or lower following a corticosteroid taper. Permanently discontinue BAVENCIO for any severe (Grade 3) immune-mediated adverse reaction that recurs and for any life-threatening (Grade 4) immune-mediated adverse reaction. The following clinically significant immune-mediated adverse reactions occurred in less than 1% of 1738 patients treated with BAVENCIO as a single agent or in 489 patients who received BAVENCIO in combination with axitinib: myocarditis including fatal cases, pancreatitis including fatal cases, myositis, psoriasis, arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid, hypopituitarism, uveitis, Guillain-Barré syndrome, and systemic inflammatory response.

BAVENCIO can cause severe or life-threatening infusion-related reactions. Premedicate patients with an antihistamine and acetaminophen prior to the first 4 infusions and for subsequent infusions based upon clinical judgment and presence/severity of prior infusion reactions. Monitor patients for signs and symptoms of infusion-related reactions, including pyrexia, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Interrupt or slow the rate of infusion for mild (Grade 1) or moderate (Grade 2) infusion-related reactions. Permanently discontinue BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Infusion-related reactions occurred in 25% of patients, including three (0.2%) patients with Grade 4 and nine (0.5%) with Grade 3.

BAVENCIO in combination with axitinib can cause major adverse cardiovascular events (MACE) including severe and fatal events. Consider baseline and periodic evaluations of left ventricular ejection fraction. Monitor for signs and symptoms of cardiovascular events. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue BAVENCIO and axitinib for Grade 3-4 cardiovascular events. MACE occurred in 7% of patients with advanced RCC treated with BAVENCIO in combination with axitinib compared to 3.4% treated with sunitinib. These events included death due to cardiac events (1.4%), Grade 3-4 myocardial infarction (2.8%), and Grade 3-4 congestive heart failure (1.8%).

BAVENCIO can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus including the risk of fetal death. Advise females of childbearing potential to use effective contraception during treatment with BAVENCIO and for at least 1 month after the last dose of BAVENCIO. It is not known whether BAVENCIO is excreted in human milk. Advise a lactating woman not to breastfeed during treatment and for at least 1 month after the last dose of BAVENCIO due to the potential for serious adverse reactions in breastfed infants.

The most common adverse reactions (all grades, ≥ 20%) in patients with metastatic Merkel cell carcinoma (MCC) were fatigue (50%), musculoskeletal pain (32%), diarrhea (23%), nausea (22%), infusion-related reaction (22%), rash (22%), decreased appetite (20%), and peripheral edema (20%).

Selected treatment-emergent laboratory abnormalities (all grades, ≥ 20%) in patients with metastatic MCC were lymphopenia (49%), anemia (35%), increased aspartate aminotransferase (34%), thrombocytopenia (27%), and increased alanine aminotransferase (20%).

The most common adverse reactions (all grades, ≥ 20%) in patients with locally advanced or metastatic urothelial carcinoma (UC) were fatigue (41%), infusion-related reaction (30%), musculoskeletal pain (25%), nausea (24%), decreased appetite/hypophagia (21%), and urinary tract infection (21%).

Selected laboratory abnormalities (Grades 3-4, ≥ 3%) in patients with locally advanced or metastatic UC were hyponatremia (16%), increased gamma-glutamyltransferase (12%), lymphopenia (11%), hyperglycemia (9%), increased alkaline phosphatase (7%), anemia (6%), increased lipase (6%), hyperkalemia (3%), and increased aspartate aminotransferase (3%).

Fatal adverse reactions occurred in 1.8% of patients with advanced renal cell carcinoma (RCC) receiving BAVENCIO in combination with axitinib. These included sudden cardiac death (1.2%), stroke (0.2%), myocarditis (0.2%), and necrotizing pancreatitis (0.2%).

The most common adverse reactions (all grades, ≥20%) in patients with advanced RCC receiving BAVENCIO in combination with axtinib (vs sunitinib) were diarrhea (62% vs 48%), fatigue (53% vs 54%), hypertension (50% vs 36%), musculoskeletal pain (40% vs 33%), nausea (34% vs 39%), mucositis (34% vs 35%), palmar-plantar erythrodysesthesia (33% vs 34%), dysphonia (31% vs 3.2%), decreased appetite (26% vs 29%), hypothyroidism (25% vs 14%), rash (25% vs 16%), hepatotoxicity (24% vs 18%), cough (23% vs 19%), dyspnea (23% vs 16%), abdominal pain (22% vs 19%), and headache (21% vs 16%).

Selected laboratory abnormalities (all grades, ≥20%) worsening from baseline in patients with advanced RCC receiving BAVENCIO in combination with axitinib (vs sunitinib) were blood triglycerides increased (71% vs 48%), blood creatinine increased (62% vs 68%), blood cholesterol increased (57% vs 22%), alanine aminotransferase increased (ALT) (50% vs 46%), aspartate aminotransferase increased (AST) (47% vs 57%), blood sodium decreased (38% vs 37%), lipase increased (37% vs 25%), blood potassium increased (35% vs 28%), platelet count decreased (27% vs 80%), blood bilirubin increased (21% vs 23%), and hemoglobin decreased (21% vs 65%).

On November 8, 2019 Aptevo Therapeutics Inc. (Nasdaq: APVO), a biotechnology company focused on developing novel immuno-oncology and hematology therapeutics and Alligator Bioscience (Nasdaq Stockholm: ATORX), a biotechnology company developing antibody-based pharmaceuticals for tumor-directed immunotherapy reported that new preclinical data for ALG.APV-527 are being presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 34th Annual Meeting at the National Harbor, Maryland, November 6-10, 2019 (Press release, Aptevo Therapeutics, NOV 8, 2019, View Source [SID1234550769]).

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ALG.APV-527 is a novel immunotherapeutic candidate intended for the treatment of a variety of 5T4-positive solid tumors. It is designed to induce signaling through the co-stimulatory receptor 4-1BB (CD137), which is present on activated cytotoxic T cells and natural killer (NK) cells. Once activated, it is designed to promote potent and selective tumor-directed immune activation in the presence of the tumor associated antigen, 5T4, which is present on many different types of solid tumors.

The preclinical data presented at SITC (Free SITC Whitepaper) show that ALG.APV-527 selectively enhances T cell and NK cell responses in the presence of 5T4 in vitro and displays potent and sustained tumor suppression in vivo. The preclinical studies demonstrate that ALG.APV-527:

Enhances CD8+ T cell and NK function and proliferation preferentially over that of CD4+ T cells, upon 5T4-mediated crosslinking
In preliminary in vivo studies in a human 4-1BB knock in model, induces rejection of established murine bladder cancer cells expressing human 5T4 at doses of 20 µg in mice and induces anti-tumor immunological memory responses
Is well tolerated after repeated dosing in a GLP toxicology study above the expected human dose and displays an antibody-like half-life of up to 9.5 days
"We’re pleased that ALG.APV-527 continues to show promising preclinical results," said Jane Gross, Ph.D., Chief Scientific Officer for Aptevo. "The ability of ALG.APV-527 to induce potent anti-tumor T cell and NK cell activity suggests 4-1BB is an attractive target for designing new immuno-oncology therapeutics. Monospecific 4-1BB-directed antibodies have been challenged by dose-limiting liver toxicities. As a novel bispecific antibody ALG.APV-527 may circumvent these challenges and minimize systemic toxicity by stimulating 4-1BB function only when co-engaged with the tumor antigen, 5T4."

"The presented preclinical data strongly support a potent effect of ALG.APV-527 without compromising on safety. The data further strengthens our CTA package and we are eagerly looking forward to discuss this candidate with potential partners to take this exciting asset further into clinical development," commented Christina Furebring, Ph.D., Vice President Preclinical Development at Alligator.

The Alligator/Aptevo poster presentation, entitled "Potent Tumor-Directed T Cell Activation and Tumor Inhibition Induced by a 4-1BB x 5T4 ADAPTIR Bispecific Antibody" is being presented on Saturday, November 9, 2019 from 7:00 am – 8:30 pm ET.

About ALG.APV-527

ALG.APV-527 is a bispecific antibody (4-1BB x 5T4) intended for tumor-directed treatment of solid cancers. ALG.APV-527 was built using Aptevo’s ADAPTIR bispecific platform and combines binding domains sourced from the ALLIGATOR-GOLD human scFv library. The ALG.APV-527 bispecific antibody consists of two parts, one part activating tumor-specific T cells through the co-stimulatory receptor 4-1BB, the other part binding to the 5T4 protein displayed on the surface of tumor cells. This enables the immune-activating effect of ALG.APV-527 to be directed specifically to the tumor and not against normal tissue.

On November 8, 2019 Cytokinetics, Incorporated (Nasdaq: CYTK) reported that it has agreed to sell an aggregate of $120.0 million principal amount of its 4.00% convertible senior notes due 2026, or the notes, in an underwritten public offering (Press release, Cytokinetics, NOV 8, 2019, View Source [SID1234550801]). Cytokinetics has granted the underwriters a 30-day option to purchase up to an additional $18.0 million aggregate principal amount of the notes in connection with the offering, solely to cover over-allotments. The aggregate principal amount of the offering was increased from the previously announced offering size of $100.0 million. The offering is expected to close on November 13, 2019, subject to customary closing conditions.

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Cytokinetics intends to use the net proceeds from the proposed offering to fund (i) the continued development of and commercial readiness activities associated with omecamtiv mecarbil, (ii) the continued clinical development of CK-274 and related compounds in indications associated with hypertrophic cardiomyopathies and related diseases associated with diastolic dysfunction and cardiac fibrosis, including heart failure with preserved ejection fraction, (iii) the continued clinical development of reldesemtiv in patients with amyotrophic lateral sclerosis and spinal muscular atrophy, including potential Phase 3 clinical trials and other commercial readiness activities, and (iv) working capital and other general corporate purposes, including tenant improvement of the new facility Cytokinetics plans to move into in 2021, capital expenditures, debt service or retirement of debt, including existing debt outstanding under Cytokinetics’ loan and security agreement. Cytokinetics also intends to use a portion of the net proceeds from the proposed offering to pay the cost of the capped call transaction described below.

The notes will be senior unsecured obligations of Cytokinetics and will bear interest at a fixed rate of 4.00% per year, payable semi-annually in arrears on May 15 and November 15 of each year, commencing on May 15, 2020. The notes will mature on November 15, 2026, unless earlier converted, redeemed or repurchased. Prior to the close of business on the business day immediately preceding July 15, 2026, the notes will be convertible at the option of the holders only upon the satisfaction of certain conditions. Thereafter, the notes will be convertible at the option of the holders at any time until the close of business on the scheduled trading day immediately before the maturity date. Upon conversion, Cytokinetics will pay or deliver, as the case may be, cash, shares of its common stock or a combination of cash and shares of its common stock, at its election. The initial conversion rate will be 94.7811 shares per $1,000 principal amount of notes (equivalent to an initial conversion price of approximately $10.55 per share), subject to adjustment upon the occurrence of specified events.

Cytokinetics may not redeem the notes prior to November 20, 2023. Cytokinetics has the right, at its election, to redeem all, or any portion, of the notes, at any time and from time to time, on a redemption date occurring on or after November 20, 2023 and, in the case of any partial redemption, on or before the 60th scheduled trading day before the maturity date, for cash, but only if the last reported sale price per share of Cytokinetics’ common stock exceeds 130% of the conversion price then in effect for a specified period of time ending on the trading day immediately before the date the notice of redemption is sent, at a redemption price equal to 100% of the principal amount of the notes to be redeemed, plus accrued and unpaid interest to, but excluding, the redemption date.

Morgan Stanley & Co. LLC and Mizuho Securities are acting as joint book-runners for the offering. JMP Securities is acting as lead manager, and H.C. Wainwright & Co. is acting as co-manager for the offering.

In connection with the pricing of the notes, Cytokinetics has entered into a privately negotiated capped call transaction (together with any additional capped call transactions entered into in connection with the exercise by the underwriters of their over-allotment option as described below, the capped call transactions), with one of the underwriters in the offering or its affiliate, or the capped call counterparty. The capped call transactions will cover, subject to customary adjustments, the number of shares of Cytokinetics’ common stock that will initially underlie the notes. The capped call transactions are generally expected to reduce the potential dilution of Cytokinetics’s common stock and/or offset any cash payments Cytokinetics is required to make in excess of the principal amount of converted notes, as the case may be, as a result of any conversion of the notes, with such reduction and/or offset subject to a cap based on the cap price. The cap price of the capped call transactions will initially be approximately $14.07 per share, which represents a premium of approximately 70% over the per share closing price of Cytokinetics’s common stock of $8.275 per share on November 7, 2019, and is subject to certain adjustments under the terms of the capped call transactions. If the underwriters in this offering exercise their over-allotment option, Cytokinetics expects to use a portion of the net proceeds from the sale of the additional notes to enter into an additional capped call transaction with the capped call counterparty.

In connection with establishing its initial hedge of the capped call transactions, the capped call counterparty or its affiliates have advised Cytokinetics that it or its affiliates expect to purchase Cytokinetics’ common stock and/or enter into various derivative transactions with respect to Cytokinetics’ common stock concurrently with, or shortly after, the pricing of the notes, including with certain investors in the notes. This activity could increase (or reduce the size of any decrease in) the market price of Cytokinetics’ common stock or the notes at that time.

In addition, the capped call counterparty or its affiliates may modify its hedge positions by entering into or unwinding various derivatives with respect to Cytokinetics’ common stock and/or purchasing or selling Cytokinetics’ common stock or other securities of Cytokinetics in secondary market transactions following the pricing of the notes and prior to the maturity of the notes (and are likely to do so on each exercise date of the capped call transaction, which are expected to occur during the 60 trading day period beginning on the 61st scheduled trading day prior to the maturity date of the notes, or following any termination of any portion of the capped call transaction in connection with any repurchase, redemption or early conversion of the notes). This activity could also cause or avoid an increase or decrease in the market price of Cytokinetics’ common stock or the notes, which could affect noteholders’ ability to convert the notes and, to the extent the activity occurs during any observation period related to a conversion of the notes, affect the amount and value of the consideration that noteholders will receive upon conversion of the notes.

An automatic shelf registration statement relating to the notes was previously filed with the Securities and Exchange Commission, or SEC, and became immediately effective on November 6, 2019. The offering will be conducted by means of a prospectus supplement and accompanying prospectus. The final prospectus supplement and the accompanying prospectus relating to and describing the terms of the proposed offering will be filed with the SEC and, when filed, will be available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus related to the offering may also be obtained by contacting: Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, New York 10014; or Mizuho Securities USA LLC, Attn: Equity Capital Markets, 320 Park Avenue, 12th Floor, New York, NY 10022-6815, by telephone (212) 205-7600, or by email: [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy the notes, nor shall there be any sale of the notes in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On November 8, 2019 IMV Inc. (TSX: IMV; NASDAQ: IMV), a clinical-stage biopharmaceutical company pioneering a novel class of immunotherapies, reported its financial and operational results for the third quarter ended September 30, 2019 (Press release, IMV, NOV 8, 2019, View Source [SID1234550824]).

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"In the third quarter and more recently, we have continued to advance our pipeline forward. In particular, we were pleased to report preliminary data at ESMO (Free ESMO Whitepaper) that highlighted DPX-Survivac’s potential to treat numerous solid tumors beyond our lead indications. Additionally, we launched a collaboration with The Wistar Institute, which applies our DPX-based targeted T cell therapy to the common BRAF mutation – another prevalent target across a range of tumor types," said Frederic Ors, President and Chief Executive Officer of IMV. "Importantly, these recent achievements reinforce our belief in the breadth of our platform and its ability to produce cancer-targeted T cells that elicit a more rapid, robust and sustained immune response. Looking ahead, we await key readouts from DPX-Survivac, including updated data from the Phase 2 study in r/r DLBCL at ASH (Free ASH Whitepaper) on December 8, 2019 and topline interim data from our Phase 1b/2 study in advanced ovarian cancer during the first quarter of next year. As we close in on proof-of-concept in these indications of high unmet medical need, we continue to believe both represent fast-to-market opportunities and are therefore preparing to launch potential pivotal studies in 2020."

DPX-Survivac Clinical Program Updates

Phase 1b/2 DeCidE1 Study in Advanced Recurrent Ovarian Cancer

DeCidE1, the Company’s Phase 1b/2 open-label study evaluating the safety and efficacy of DPX-Survivac and intermittent low-dose cyclophosphamide (CPA), with and without Epacadostat, in advanced recurrent ovarian cancer, is ongoing without Epacadostat.

Enrollment is complete in this study and the Company intends to report topline interim data during Q1 2020.

Phase 2 SPiReL Study in Recurrent/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

SPiReL, an investigator-sponsored Phase 2 study evaluating DPX-Survivac and ildCPA in combination with Keytruda (pembrolizumab) in recurrent/refractory DLBCL is ongoing.

Neil Berinstein, M.D. FRCPC, ABIM, Hematologist at the Sunnybrook Health Science Centre will deliver a poster presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on December 8, 2019, including updated data from the study.

As of November 7, 2019, 17 patients have been enrolled across five different clinical sites in Canada. The non-randomized, open label study is expected to enroll 25 evaluable participants in Canada. Additional patients are being screened and topline data are expected from this study in the first half of 2020.

Phase 2 Basket Trial in Multiple Advanced and Metastatic Solid Tumors

In September 2019, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress in Barcelona, Spain, IMV presented preliminary results from its ongoing Phase 2 basket trial, evaluating DPX-Survivac and intermittent low-dose CPA in combination with pembrolizumab in patients with advanced and metastatic solid tumors.

As of the data cut-off, 23 patients had been treated across all five patient cohorts with bladder, hepatocellular carcinoma (liver), ovarian, and non-small cell lung (NSCLC) cancers, as well as tumors shown to be positive for the microsatellite instability high (MSI-H) biomarker. Preliminary results from the first on-study scan showed signs of clinical activity with tumor regressions observed in patients with ovarian, non-small cell lung and bladder cancers, including two partial responses, and a consistent safety profile including no grade 3-4 immune-related adverse events. The preliminary data are available here.

As of November 7, 2019, 13 clinical sites have been activated, 64 patients are screened, and 31 patients have been enrolled. The study continues to enroll patients towards a total enrollment target of 184 patients across all five cohorts. The Company expects to report topline data in the first half of 2020.

Operational Highlights:

Appointment of Joanne Schindler, M.D., D.V.M. as Chief Medical Officer. Dr. Schindler joined IMV in November 2019 with over 15 years of experience in the biopharmaceutical industry, primarily in early-stage oncology drug development. Most recently, she served as Vice President, Clinical Development and Executive Medical Director at H3 Biomedicine, where she oversaw clinical development strategy and execution.

Research collaboration with Meenhard Herlyn, D.V.M., D.Sc. and The Wistar Institute to develop a targeted T cell therapy against the BRAF mutation. Under this collaboration, IMV will optimize the DPX formulation with Wistar-identified peptides targeting BRAF, one of the most frequently identified cancer-causing mutations in melanoma and various other cancers, including non-Hodgkin’s lymphoma, colorectal cancer, thyroid cancer, and non-small cell lung and ovarian carcinomas. IMV holds an exclusive option to in-license intellectual property related to the program.

Upcoming Milestones:

Over the course of upcoming quarters, the Company expects to deliver the following milestones:

Updated results from Phase 2 SPiReL trial (DLBCL) at ASH (Free ASH Whitepaper) 2019 on December 8, 2019
Topline results from Phase 1b/2 DeCidE1 trial (ovarian) during Q1 2020
Topline results from Phase 2 SPiReL trial (DLBCL) in 1H 2020
Topline results from Phase 2 basket trial (multiple tumors) of DPX-Survivac in 1H 2020.
Overview of Q3 2019 Financial Results (In Canadian dollars)

At September 30, 2019, the Corporation had cash and cash equivalents of $21.4 million and working capital of $21.2 million, compared with $14.9 million and $12.2 million, respectively at December 31, 2018. Management believes that the Corporation’s cash resources of $21.4 million and its additional potential cash resources of $2.3 million will be sufficient to fund operations for the next twelve months.

For the nine-month period ended September 30, 2019, IMV’s cash burn rate (defined as net loss and comprehensive loss adjusted for charges to operations not involving cash as described in the statement of cash flows) was $17.4 million. Based on the current business plan, the Corporation forecasts the quarterly cash burn rate to be between $5 million and $6 million for the fourth quarter of 2019.

The net loss and comprehensive loss of $7.9 million ($0.16 per share) for the three-month period ended September 30, 2019, was $1.9M higher than the net loss and comprehensive loss for three-month period ended September 30, 2018. This relates mainly to an increase in R&D expenses of $1.8M related to the basket trial and pre-clinical preparation for a phase I trial with DPX-SurMAGE.

For the nine-month period ended September 30 2019, the net loss and comprehensive loss of $18.9M ($0.38 per share) was $4.6M higher than the net loss and comprehensive loss for the nine-month period ended September 30 2018. This relates mainly to an increase in R&D expenses of $5.1M related to the basket trial and the preparation for a phase I trial with DPX-SurMAGE.

As of November 7, 2019, the number of issued and outstanding common shares was 50,630,875 and a total of 1,932,080 stock options, warrants, and deferred share units were outstanding.

The Corporation’s unaudited interim condensed consolidated results of operations, financial condition and cash flows for the three and nine-months ended September 30, 2019 and the related management’s discussion and analysis (MD&A) are available on SEDAR at www.sedar.com and on EDGAR at www.sec.gov/edgar.

Conference Call and Webcast Information

Management will host conference call and webcast this morning, November 8, 2019 at 8:00 am ET. Financial analysts are invited to join the conference call by dialing (844) 461-9932 (U.S. and Canada) or (636) 812-6632 (international) using the conference ID# 6590953. Other interested parties will be able to access the live audio webcast at this link: View Source

On November 8, 2019 AIVITA Biomedical, Inc., a biotech company specializing in innovative stem cell applications, reported that new data from its ongoing Phase 2 clinical trial in glioblastoma multiforme will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting by Lead Principal Investigator Dr. Daniela Bota (Press release, AIVITA Biomedical, NOV 8, 2019, View Source [SID1234550754]). The podium presentation will detail early encouraging survival data, immune response data and tumor biomarker and imaging data. Details for the oral presentation are as follows:

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Meeting: Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting
Presenter: Dr. Daniela Bota, MD, PhD, University of California, Irvine; AIVITA GBM Lead Principal Investigator
Title: Phase II trial of therapeutic vaccine consisting of autologous dendritic cells loaded with autologous tumor cell antigens from self-renewing cancer cells in patients with newly diagnosed glioblastoma
Session: Session 311: A Tale of Two Brain Tumors: Primary versus Metastatic CNS Tumors
When: 6:15 PM ET, Saturday Nov 9
Location: Gaylord National Hotel & Convention Center, National Harbor, MD