On August 6, 2021 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi reported the Phase 3 trial of PD-1 inhibitor Libtayo in combination with platinum-doublet chemotherapy was stopped early after meeting its overall survival (OS) primary endpoint in patients with advanced non-small cell lung cancer (NSCLC) (Press release, Regeneron, AUG 6, 2021, View Source [SID1234586038]). Adding Libtayo to chemotherapy significantly improved OS, compared to chemotherapy alone, in the trial that enrolled patients with metastatic or locally advanced disease and tumors with either squamous or non-squamous histology and across all PD-L1 expression levels. These data are planned to form the basis of regulatory submissions in the U.S. and European Union.

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"Libtayo in combination with chemotherapy increased median overall survival to 22 months in patients with advanced non-small cell lung cancer, compared to 13 months with chemotherapy alone," said Miranda Gogishvili, M.D., an oncologist at the High Technology Medical Center, University Clinic, in Tbilisi, Georgia and a trial investigator. "Notably, the Phase 3 trial enrolled patients with a variety of challenging-to-treat disease characteristics, as well as those with locally advanced disease. These data add to the growing body of evidence supporting Libtayo in advanced non-small cell lung cancer, which also include the pivotal results for Libtayo monotherapy in cases of high PD-L1 expression."

The decision to stop the trial early was based on a recommendation by the Independent Data Monitoring Committee (IDMC) during a protocol-specified interim analysis. In this top-line initial analysis of 466 patients, combining Libtayo with chemotherapy reduced the risk of death by 29% compared to chemotherapy alone (hazard ratio: 0.71; 95% confidence interval [CI]: 0.53-0.93; p=0.014). Median OS was 22 months (95% CI: 16 months to not evaluable) for Libtayo and chemotherapy, and 13 months (95% CI: 12 to 16 months) for chemotherapy alone. No new Libtayo safety signals were identified in the IDMC analysis, and additional detailed efficacy and safety data will be presented at an upcoming medical meeting.

Lung cancer is the leading cause of cancer death worldwide. In 2020, an estimated 2.2 million and 225,000 new cases were diagnosed globally and in the U.S., respectively. Approximately 84% of all lung cancers are NSCLC, with 75% of these cases diagnosed in advanced stages. While PD-1 inhibitor monotherapy has primarily advanced the treatment of NSCLC with ≥50% PD-L1 expression, approximately 70% of all NSCLC cases will have <50% PD-L1 expression, making it the most common treatment setting.

The use of Libtayo in combination with chemotherapy for advanced NSCLC is currently under clinical investigation, and its safety and efficacy have not been fully evaluated by any regulatory authority.

About the Phase 3 Trial
The randomized, multicenter Phase 3 trial, called EMPOWER-Lung 3, investigated a first-line combination treatment of Libtayo and platinum-doublet chemotherapy, compared to platinum-doublet chemotherapy alone, in squamous or non-squamous advanced NSCLC irrespective of PD-L1 expression. Specifically, the trial included 466 patients who tested negative for ALK, EGFR and ROS1 mutations and had either previously untreated metastatic NSCLC (stage IV) or locally advanced NSCLC (stage IIIB/C) and were not candidates for definitive chemoradiation.

Patients were randomized 2:1 to receive either Libtayo 350 mg (n=312) or placebo (n=154) administered intravenously every three weeks for 108 weeks, plus platinum-doublet chemotherapy administered every three weeks for four cycles. The co-primary endpoints were OS and progression-free survival, and key secondary endpoints included objective response rate and best overall response.

Among trial patients, 30% (n=139) had tumors with <1% PD-L1 expression, 38% (n=175) had tumors with 1% to 49% PD-L1 expression, and 33% (n=152) had tumors with ≥50% PD-L1 expression.

About Libtayo
Libtayo is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T-cells. By binding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation.

The generic name for Libtayo in its approved U.S. indications is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. FDA. Libtayo is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.

The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. Libtayo is currently being investigated in advanced cervical cancer, as well as in trials combining Libtayo with either conventional or novel therapeutic approaches for other solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.

About Regeneron’s VelocImmune Technology
Regeneron’s VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron’s President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create approximately a quarter of all original, FDA-approved fully human monoclonal antibodies currently available. This includes REGEN–COV (casirivimab and imdevimab), Dupixent (dupilumab), Libtayo (cemiplimab-rwlc), Praluent (alirocumab), Kevzara (sarilumab), Evkeeza (evinacumab-dgnb) and Inmazeb (atoltivimab, maftivimab and odesivimab-ebgn).

IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS

What is Libtayo?
Libtayo is a prescription medicine used to treat people with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC) that has spread or cannot be cured by surgery or radiation.

Libtayo is a prescription medicine used to treat people with a type of skin cancer called basal cell carcinoma that cannot be removed by surgery (locally advanced BCC) and have received treatment with an HHI, or cannot receive treatment with a HHI.

Libtayo is a prescription medicine used to treat people with a type of skin cancer called basal cell carcinoma that has spread (metastatic BCC) and have received treatment with a hedgehog pathway inhibitor (HHI), or cannot receive treatment with a HHI. This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit.

Libtayo is a prescription medicine used to treat people with a type of lung cancer called non-small cell lung cancer (NSCLC). Libtayo may be used as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or your lung cancer has spread to other areas of your body (metastatic lung cancer), and your tumor tests positive for high "PD-L1" and your tumor does not have an abnormal "EGFR"," ALK "or "ROS1" gene.

It is not known if Libtayo is safe and effective in children.

What is the most important information I should know about Libtayo?
Libtayo is a medicine that may treat certain cancers by working with your immune system. Libtayo can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including:

Lung problems: cough, shortness of breath, or chest pain
Intestinal problems: diarrhea (loose stools) or more frequent bowel movements than usual, stools that are black, tarry, sticky or have blood or mucus, or severe stomach-area (abdomen) pain or tenderness
Liver problems: yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach area (abdomen), dark urine (tea colored), or bleeding or bruising more easily than normal
Hormone gland problems: headache that will not go away or unusual headaches, eye sensitivity to light, eye problems, rapid heartbeat, increased sweating, extreme tiredness, weight gain or weight loss, feeling more hungry or thirsty than usual, urinating more often than usual, hair loss, feeling cold, constipation, your voice gets deeper, dizziness or fainting, or changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
Kidney problems: decrease in your amount of urine, blood in your urine, swelling of your ankles, or loss of appetite
Skin problems: rash, itching, skin blistering or peeling, painful sores or ulcers in mouth or nose, throat, or genital area, fever or flu-like symptoms, or swollen lymph nodes
Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with Libtayo. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include: chest pain, irregular heartbeat, shortness of breath or swelling of ankles, confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs, double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight, persistent or severe muscle pain or weakness, muscle cramps, low red blood cells, or bruising
Infusion reactions that can sometimes be severe. Signs and symptoms of infusion reactions may include: nausea, chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, feel like passing out, fever, back or neck pain, or facial swelling.
Rejection of a transplanted organ. Your healthcare provider should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had.
Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with Libtayo. Your healthcare provider will monitor you for these complications.
Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with Libtayo. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with Libtayo if you have severe side effects.

Before you receive Libtayo, tell your healthcare provider about all your medical conditions, including if you:

have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
have received an organ transplant
have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
are pregnant or plan to become pregnant. Libtayo can harm your unborn baby
Females who are able to become pregnant:

Your healthcare provider will give you a pregnancy test before you start treatment.
You should use an effective method of birth control during your treatment and for at least 4 months after your last dose of Libtayo. Talk with your healthcare provider about birth control methods that you can use during this time.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Libtayo.
are breastfeeding or plan to breastfeed. It is not known if Libtayo passes into your breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose of Libtayo.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Libtayo include muscle or bone pain, tiredness, rash, and diarrhea. These are not all the possible side effects of Libtayo. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Regeneron Pharmaceuticals and Sanofi at 1-877-542-8296.

On August 6, 2021 Akeso, Inc. (9926.HK, the "Company" or "Akeso") reported that the anti PD-1 monoclonal antibody drug Penpulimab monoclonal antibody injection co-developed by the Company with Sino Biopharmaceutical Limited (stock code: 1177.HK), has obtained marketing approval by the National Medical Products Administration (the "NMPA") of China, for treatment of patients with relapsed or refractory ("r/r") classic Hodgkin’s lymphoma ("cHL") after at least second-line systemic chemotherapy treatment (Press release, Akeso Biopharma, AUG 6, 2021, View Source [SID1234586029]).

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This approval of Penpulimab by the NMPA is based on a multicenter, single-arm, open-label pivotal clinical trial. Patients enrolled were r/r cHL patients who had failed at least second- line systemic chemotherapy and were administered 200 mg Penpulimab monoclonal antibody by intravenous injection once every two weeks until progress is made or reached unacceptable toxicity. The key research endpoint was the objective response rate ("ORR") evaluated by the independent radiology review committee ("IRRC") with reference to the Lugano 2014 lymphoma efficacy rating criteria.

The research shows that:

The ORR assessed by IRRC was 89.4% (76/85) with 47.1% (40/85) patients achieved complete response (CR). The median follow-up time was 15.8 months. The 12-month duration of response ("DoR") was 74.9%. And 12-month progression-free survival ("PFS") was 72.1%.
In terms of safety profile, the median exposure to Penpulimab antibody was 14.8 months, and 76.6% of patients were treated with Penpulimab antibody for 12 months or longer. Serious adverse events ("SAEs") associated with Penpulimab antibody was 10.6%, with no more than one patient experiencing a drug-related SAE. 26.6% of Grade 3 or higher adverse reactions had occurred, with equal to or greater than 2% of rash, hyperlipidemia, and lung infection. 4.3% of Grade 3 immune-related adverse events ("irAEs") had occurred, with no Grade 3 or higher irAEs.
Penpulimab is currently the only new PD-1 monoclonal antibody that applies IgG1 subtype and is modified by Fc segment, which has a lower antigen binding dissociation rate and a unique binding epitope as demonstrated by analysis on crystal structure. These features allow Penpulimab to effectively and continuously block PD-1/PD-L1 binding, thus differentiates it from other PD-1 products on the market, and may allow Penpulimab to more effectively enhance immunotherapeutic efficacy and reduce immune-related adverse reactions, as demonstrated by improved safety profile in clinical data.

Penpulimab is Akeso’s first innovative antibody protein drug that has been granted marking approval with major research studies covering major oncology diseases such as liver cancer, gastric cancer, lung cancer, Hodgkin’s lymphoma and nasopharyngeal carcinoma. In addition to the said approval for the treatment of cHL, Penpulimab has submitted 2 NDAs in China and 1 biologics license application ("BLA") in the U.S.:

In August 2021, NDA of Penpulimab for third-line treatment of metastatic nasopharyngeal carcinoma was submitted and was accepted by the NMPA.

In July 2021, NDA of Penpulimab for combined chemotherapy for first-line treatment of locally advanced or metastatic squamous non-small-cell lung cancer was submitted and was accepted by the NMPA.

In May 2021, Penpulimab for third-line treatment of metastatic nasopharyngeal carcinoma has been submitted to the Food and Drug Administration of the United States (FDA) for a BLA through the Real-Time Oncology Review (RTOR) program.

On August 6, 2021 BioInvent International AB ("BioInvent") (Nasdaq Stockholm: BINV) reported that it has entered into a second clinical trial collaboration and supply agreement with MSD, a tradename of Merck & Co., Inc., Kenilworth, NJ., USA, to evaluate the combination of BioInvent’s BI-1808, one of its proprietary anti-TNFR2 antibodies and MSD’s anti-PD-1 therapy, KEYTRUDA in a Phase 1/2a clinical trial for patients with lung cancer and ovarian cancer (Press release, BioInvent, AUG 6, 2021, View Source [SID1234586028]).

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"We are very pleased we have reached a second collaboration with MSD that supports the expansion of the clinical trial program with our anti-TNFR2 antibody BI-1808. The Phase 1 component is already enrolling patients who receive BI-1808 as a single agent. We are excited about the potential synergistic activity of BI-1808 in combination with pembrolizumab and this agreement supports the strong interest elicited by our broadening pipeline of anti-cancer antibodies," said Martin Welschof, CEO of BioInvent.

The Phase 1/2a trial explores the potential of BI-1808 to treat patients with ovarian cancer and non-small cell lung cancer both as a single agent and in combination with KEYTRUDA. A separate cohort in the Phase 2a component will explore the activity of BI-1808 as a single agent in cutaneous T cell lymphoma. It is planned to perform the trial in the U.S., Denmark, Hungary, the United Kingdom, and Russia. Patient enrollment is already taking place in several European countries.

The anti-TNFR2 antibody BI-1808 is part of BioInvent’s tumor-associated regulatory T cells (Treg)-targeting program, which has emerged from its F.I.R.S.T platform technology that simultaneously identifies targets and high-quality antibodies, generating promising new drug candidates to target the tumor microenvironment. TNFR2 is particularly upregulated on Tregs and has been shown to be important for tumor expansion and survival, representing a new and important target for cancer immunotherapies.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

On August 6, 2021 Immunic, Inc. (Nasdaq: IMUX), a clinical-stage biopharmaceutical company developing a pipeline of selective oral immunology therapies focused on treating chronic inflammatory and autoimmune diseases, reported financial results for the second quarter ended June 30, 2021 and highlighted recent activity (Press release, Immunic, AUG 6, 2021, View Source [SID1234586027]).

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"So far this year, we have made outstanding progress with both our selective oral DHODH inhibitor, IMU-838, as well as IMU-935, a highly potent and selective inverse agonist of the transcription factor RORγt, enabling what we believe will be an eventful and potentially transformative first half of 2022. In particular, we anticipate five data read-outs from clinical trials within the next twelve months, and expect to begin our first phase 3 program very soon. I want to congratulate our entire team for this remarkable momentum," stated Daniel Vitt, Ph.D., Chief Executive Officer and President of Immunic. "In June, we received U.S. Food and Drug Administration (FDA) clearance for our Investigational New Drug (IND) application for the phase 3 ENSURE program of IMU-838 in patients with relapsing-remitting multiple sclerosis (RRMS), and the supportive phase 2 CALLIPER trial in patients with progressive multiple sclerosis (PMS). Initiation of these trials in the second half of this year will mark a major milestone for our lead program. Additionally, we look forward to completing recruitment of our ongoing phase 2 CALDOSE-1 trial of IMU-838 in patients with ulcerative colitis (UC) during the second half of 2021, and reporting top-line data for this potential second key indication for IMU-838 in the first half of 2022."

"At our virtual R&D Day just last month, we presented very encouraging in vitro data showing that IMU-935 may inhibit both the generation of Th17 cells and the production of IL-17 cytokines that are responsible for the development of autoimmune diseases, without impairing thymocyte development, thereby avoiding a potential risk for lymphoma that has complicated third-party programs in this space. We also detailed highly encouraging new preclinical data which suggests that IMU-935 can affect castration-resistant prostate cancer (CRPC) both directly by reducing androgen receptor (AR) expression via RORγ and inhibiting tumor growth, and indirectly by inhibiting tumorigenesis-promoting Th17 and IL-17. Based on the strength of this data, we are preparing a phase 1 trial in metastatic CRPC (mCRPC) patients with Johann Sebastian de Bono, M.D., Ph.D., Regius Professor of Cancer Research and Professor in Experimental Cancer Medicine, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom, acting as the Principal Investigator. We expect this trial to commence during the fourth quarter of this year and also anticipate availability of initial human data from moderate-to-severe psoriasis patients from our phase 1 trial of IMU-935 during the second quarter of 2022."

Dr. Vitt added, "As previously announced, at the end of the first quarter of 2021, we settled our remaining royalty obligation to 4SC AG for both IMU-838 and IMU-935, for $17.3 million, which was paid 50% in cash and 50% in shares of Immunic’s common stock during the second quarter. This strategic decision provides us with 100% of the future sales potential of our two lead programs and should drive significant value for our shareholders. Last month, we were able to offset this payment by bolstering our balance sheet with a $45.0 million financing, providing us with anticipated runway through multiple value inflection points into 2023."

Second Quarter 2021 and Subsequent Highlights

July 2021: Completed a $45.0 million underwritten public offering of common stock.
July 2021: Hosted a virtual R&D Day to provide an update on the preclinical and clinical development of IMU-935, including:
Based on preclinical studies performed by Immunic, as well as third-party research, the company believes that IMU-935’s observed selectivity may enable it to inhibit the generation of Th17 cells and the production of IL-17 cytokines without impairing RORγt function required for normal thymocyte development and may, therefore, avoid the risk of T cell malfunction and potential lymphoma formation seen in third-party RORγt programs.
In preclinical studies, IMU-935 was observed to suppress the expression of mutated AR-V7 in prostate cancer cell lines, thus potentially inhibiting tumor growth in CRPC patients who are insensitive to androgen-targeted therapies. By suppressing the expression of pro-tumorigenic IL-17, IMU-935 may also inhibit tumorigenesis in an indirect fashion. Based on these results, the company is currently preparing an open-label phase 1 dose escalation trial designed to establish a recommended phase 2 dose and to assess safety, tolerability, anti-tumor activity, biomarkers and pharmacokinetics (PK) of IMU-935 in patients with progressive mCRPC.
The full PK and blinded safety data from the completed single ascending dose (SAD) part of the phase 1 trial of IMU-935 was made available. The data set revealed dose-linear PK and a blood half-life that may be appropriate for once or twice daily dosing. Although the trial is still blinded, no significant safety findings have been detected in the SAD cohorts, to date.
June 2021: Announced FDA clearance of the company’s IND application to begin the phase 3 ENSURE program, comprised of two multicenter, randomized, double-blind trials designed to evaluate the efficacy, safety, and tolerability of IMU-838 versus placebo in RRMS patients. Additionally, announced FDA clearance of a separate IND application to initiate the supportive, multicenter, randomized, double-blind, placebo-controlled phase 2 CALLIPER trial of IMU-838 in patients with PMS, which will run concurrently with the phase 3 program in RRMS and which is designed to corroborate IMU-838’s neuroprotective potential.
June 2021: Announced the appointment of Inderpal Singh as General Counsel. Mr. Singh is responsible for legal and compliance matters and has become part of the management team of the company.
April 2021: Announced interim data from the 10 mg Cohort 2 of the EMPhASIS trial of IMU-838 in RRMS confirming, along with previously published data from Cohort 1, that the 30 mg once daily dosing of IMU-838 is the most appropriate dose for the company’s phase 3 program in RRMS. The experimental part of double-blind treatment in Cohort 2 has meanwhile been completed.
Anticipated Clinical Milestones

IMU-838 in RRMS: The twin, multicenter, randomized, double-blind, phase 3 ENSURE-1 and ENSURE-2 trials of 30 mg daily IMU-838 or placebo will run concurrently. Dosing of the first patient is expected in the second half of 2021.
IMU-838 in PMS: The multicenter, randomized, double-blind, phase 2 CALLIPER trial of 45 mg daily IMU-838 or placebo is intended to run concurrently with and to complement the phase 3 program in RRMS. Dosing of the first patient is expected in the third quarter of 2021.
IMU-838 in UC: Recruitment of the phase 2 CALDOSE-1 trial of IMU-838 in patients with UC is expected to be completed in the second half of 2021 and top-line data of the induction phase is expected to be available in the first half of 2022, as previously announced.
IMU-935 phase 1 program in healthy volunteers and psoriasis patients: The multiple ascending dose (MAD) part of the phase 1 trial of IMU-935 is ongoing and progressing. Unblinded safety, pharmacodynamic and PK data from the SAD and MAD parts in healthy volunteers is expected to be available in the second half of 2021. Initiation of the third portion of the phase 1 trial in patients with moderate-to-severe psoriasis is expected in the third quarter of 2021 and initial human data from this patient population is expected to be available in the second quarter of 2022.
IMU-935 phase 1 trial in CRPC patients: An open-label phase 1 dose escalation trial designed to establish a potential recommended phase 2 dose and to assess safety, tolerability, anti-tumor activity, biomarkers and PK of IMU-935 in patients with progressive mCRPC, is expected to commence in the fourth quarter of 2021.
IMU-856 phase 1 program: The SAD part of the ongoing phase 1 trial of IMU-856 has been completed. Based on the favorable data available so far, the company expects to receive clearance from the Ethics Committee in Australia to proceed to the MAD part in healthy volunteers, in the near future. Unblinded safety data from the SAD and MAD parts in healthy volunteers is expected to be available in the first quarter of 2022. Initiation of the third portion of the phase 1 trial in patients with several diseases involving bowel barrier dysfunction is expected in the first half of 2022.
Financial and Operating Results

Research and Development (R&D) Expenses were $15.7 million for the three months ended June 30, 2021, as compared to $10.0 million for the same period ended June 30, 2020. The $5.7 million increase was primarily due to (i) a $2.6 million increase in preparation costs related to the phase 3 program of IMU-838 in multiple sclerosis, (ii) a $1.8 million increase in external development costs related to the phase 2 clinical trial of IMU-838 in patients with UC, (iii) a $1.7 million increase in preparation costs related to the phase 2 trial of IMU-838 in PMS, (v) a $0.6 million increase in external development costs related to the phase 1 clinical trial of IMU-935, (vi) a $0.5 million increase in external development costs related to the phase 1 clinical trial of IMU-856, (vii) a $0.7 million increase in personnel expenses in research and development and (viii) $0.1 million related to increased costs across numerous categories. The increases were partially offset by a decrease of $2.3 million related to drug supply costs for IMU-838, IMU-935 and IMU-856.

For the six months ended June 30, 2021, R&D expenses were $27.3 million, as compared to $16.4 million for the same period ended June 30, 2020. The $10.9 million increase was primarily attributable to (i) a $2.9 million increase in preparation costs related to the phase 3 program of IMU-838 in multiple sclerosis, (ii) a $2.4 million increase in preparation costs related to the phase 2 trial of IMU-838 in PMS, (iii) a $2.2 million increase in external development costs related to the phase 2 clinical trial of IMU-838 in patients with UC, (iv) a $1.4 million increase in external development costs related to the phase 2 clinical trial in patients with COVID-19 as trials did not start until the second quarter of 2020, (v) a $0.8 million increase in external development costs related to the phase 1 clinical trial of IMU-856, (vi) a $0.7 million increase in external development costs related to the phase 1 clinical trial of IMU-935, (vii) a $1.0 million increase in personnel expenses in research and development and (viii) $1.0 million related to increased costs across numerous categories. The increases were partially offset by a decrease of $1.5 million in drug supply costs for IMU-856.
General and Administrative (G&A) Expenses were $3.4 million for the three months ended June 30, 2021, as compared to $2.2 million for the same period ended June 30, 2020. The $1.2 million increase was primarily due to (i) a $0.7 million increase related to non-cash stock compensation expense, (ii) a $0.3 million increase of legal and consultancy costs and (iii) a $0.2 million increase across numerous categories.

For the six months ended June 30, 2021, G&A expenses were $7.1 million, as compared to $4.8 million for the same period ended June 30, 2020. The $2.3 million increase was primarily due to (i) a $1.7 million increase related to non-cash stock compensation expense and (ii) a $0.6 million increase across numerous categories, primarily for legal and consultancy services.
4SC Royalty Settlement: On March 31, 2021, Immunic AG and 4SC AG entered into a Settlement Agreement, pursuant to which Immunic AG settled its remaining obligation of a 4.4% royalty on net sales of IMU-838, for $17.25 million. The payment was made 50% in cash and 50% in shares of Immunic’s common stock. No further payment obligations remain between Immunic and 4SC AG.
Other Income was $1.2 million for the three months ended June 30, 2021, as compared to $0.8 million for the same period ended June 30, 2020. The $0.4 million increase was primarily attributable to (i) a $0.6 million foreign exchange gain on a $52.0 million intercompany loan between Immunic, Inc. and Immunic AG (the "Intercompany Loan") and (ii) a $0.3 million increase in research and development tax incentives for clinical trials in Australia as a result of increased spending on clinical trials in Australia. The increase was partially offset by a $0.5 million decrease in recognized deferred income attributable to reimbursements of research and development expenses in connection with the option agreement with Daiichi Sankyo Co., Ltd. realized in the second quarter of 2020.

For the six months ended June 30, 2021, other income was $(1.0) million, as compared to $1.3 million for the same period ended June 30, 2020. The $2.3 million decrease was primarily attributable to (i) a $1.9 million foreign exchange loss on the Intercompany Loan and (ii) a $1.0 million decrease in recognized deferred income attributable to reimbursements of research and development expenses in connection with the Daiichi Sankyo Agreement realized in the first six months of 2020. The decrease was partially offset by a $0.6 million increase in research and development tax incentives for clinical trials in Australia as a result of increased spending on clinical trials in Australia.
Net Loss for the three months ended June 30, 2021, was approximately $17.9 million, or $0.82 per basic and diluted share, based on 21,749,439 weighted average common shares outstanding, compared to a net loss of approximately $11.5 million, or $0.90 per basic and diluted share, based on 12,695,989 weighted average common shares outstanding for the same period ended June 30, 2020.

Net loss for the six months ended June 30, 2021 was approximately $52.5 million, or $2.44 per basic and diluted share, based on 21,463,656 weighted average common shares outstanding, compared to a net loss of approximately $19.9 million, or $1.70 per basic and diluted share, based on 11,722,725 weighted average common shares outstanding for the same period ended June 30, 2020.
Cash and Cash Equivalents as of June 30, 2021, were $87.2 million, which does not include the approximately $42.2 million raised in the equity offering on July 19, 2021. Management expects its current cash and cash equivalents to be sufficient to fund operations into 2023.

On August 6, 2021 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported its financial results and development highlights for the quarter ended June 30, 2021 (Press release, Oncolytics Biotech, AUG 6, 2021, View Source [SID1234586026]). All dollar amounts are expressed in Canadian currency unless otherwise noted.

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"Our second quarter accomplishments have advanced our lead clinical breast cancer program down a clear path towards a registrational study and substantially de-risked our broader clinical pipeline," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics Biotech Inc. "Clinical AWARE-1 data show that pelareorep is an immunotherapeutic agent that synergistically combines with checkpoint inhibitors. These findings support the statistically significant overall survival benefit observed in our prior phase 2 breast cancer trial, achieving a key regulatory objective. They also suggest that pelareorep’s efficacy can be further enhanced by combining it with checkpoint inhibition. We are currently working to confirm this hypothesis in the BRACELET-1 breast cancer trial, which will support pelareorep’s advancement to a registrational study."

Dr. Coffey continued, "Beyond our lead program, we also presented clinical proof-of-concept data in pancreatic cancer that further demonstrate pelareorep’s immunologic mechanism of action and potential to address unmet needs across multiple indications. Together with AWARE-1 data, these results support our ongoing trials evaluating pelareorep-checkpoint inhibitor combinations and highlight pelareorep’s potential as an enabling technology for multiple classes of immunotherapeutic agents. Looking forward, our strong financial foundation leaves us well-positioned to build on this momentum and advance pelareorep’s clinical development. As we work towards this goal, we will remain primarily focused on breast cancer and our stated clinical milestones while pursuing a partnership strategy to further broaden pelareorep’s potential impact."

Second Quarter and Subsequent Highlights

Breast Cancer Program

Achieved primary endpoint in AWARE-1 study

Data from the twenty HR+/HER2- early-stage breast cancer patients included in AWARE-1’s first two cohorts were presented in an electronic poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 (link to PR; link to poster). Results from these patients, who were treated with pelareorep and letrozole without (cohort 1) or with (cohort 2) the PD-L1 inhibitor atezolizumab (Tecentriq), showed that that pelareorep and letrozole treatment upregulated tumor PD-L1 expression, induced the generation and expansion of T cell clones, promoted tumor infiltration of CD8+ T cells, and increased CelTIL score, a measure of tumor cellularity and inflammation that is significantly correlated with event-free and overall survival. These desirable effects were further enhanced in patients receiving atezolizumab, demonstrating that pelareorep and atezolizumab synergistically combine to generate an anti-cancer immune response in the tumor and peripheral blood. Notably, cohort 2 met the pre-specified success criteria for the study’s primary endpoint, with six of ten patients achieving at least a 30% increase in CelTIL score following treatment. Together, these data support the results of a prior successful phase 2 trial (IND-213) that showed a statistically significant near doubling of overall survival with pelareorep treatment. This supports the clinical rationale behind the phase 2 BRACELET-1 trial: Evaluating the safety and efficacy of pelareorep and chemotherapy alone, and in combination with a PD-L1 inhibitor, in HR+/HER2- breast cancer patients.

Gastrointestinal Cancers Program

Phase 2 data demonstrating clinical proof-of-concept for pelareorep-checkpoint inhibitor combination therapy in pancreatic cancer

Data from a phase 2 trial evaluating pelareorep in combination with the PD-1 inhibitor pembrolizumab (KEYTRUDA) in pancreatic adenocarcinoma patients who progressed after first-line treatment were featured in an electronic poster presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (link to PR; link to poster). Findings from the trial indicate that pelareorep and pembrolizumab synergize and show anti-cancer activity in these difficult-to-treat patients, with a 42% disease control rate achieved and durations of control ranging from approximately 2.5 months to approximately 7 months despite the absence of chemotherapy in the treatment regimen. Biomarker data showed that patients achieving disease control had increased activation of anti-cancer CD8+ T cells in the peripheral blood, and reduced levels of pro-tumor Treg cells in the peripheral blood and tumor compared to those with progressive disease. These results, which are consistent with what has been seen in clinical trials in other indications, such as breast cancer, highlight the broad applicability of pelareorep’s immunotherapeutic mechanism of action. They also bode well for a successful outcome in the phase 1/2 GOBLET trial, which includes a cohort evaluating pelareorep and the PD-L1 inhibitor atezolizumab in combination with chemotherapy as a first-line treatment in metastatic pancreatic cancer patients (link to PR).

Additional Immunotherapeutic Combinations and Opportunities

Preclinical data highlighting pelareorep’s ability to synergize with multiple classes of anti-cancer agents

Data presented in two electronic poster presentations at the AACR (Free AACR Whitepaper) Annual Meeting 2021 showed that pelareorep enhanced the anti-tumor efficacy of the poly(ADP)-ribose polymerase 1 (PARP-1) inhibitor talazoparib and the cyclin-dependent kinase (CDK) 4/6 inhibitor palbociclib, which are both FDA approved for the treatment of breast cancer. The observed synergistic effects were notably mediated through immunologic mechanisms rather than through the molecular pathways typically associated with PARP-1 and CDK4/6 inhibition (link to PR; link to CDK4/6 poster; link to PARP-1 poster). Together, these results suggest that pelareorep may enhance the therapeutic potential of PARP-1 and CDK4/6 inhibitors by expanding the mechanisms by which they exert anti-tumor effects.

Changes to the Board of Directors

William G. Rice, Ph.D. has stepped down from Oncolytics Biotech’s Board of Directors to avoid any potential conflicts that might arise from the development of pelareorep with molecules being developed by Aptose Biosciences Inc., the company for which Dr. Rice serves as Chairman of the Board, President & Chief Executive Officer. "I’m a staunch supporter of Oncolytics and wish to express my sincere gratitude for the time serving the Board and working with a wonderful group of directors and officers," stated Dr. Rice. Oncolytics would like to thank Dr. Rice for his guidance during his tenure as a member of the Board.

Financial Highlights

As of June 30, 2021, the Company reported $50.8 million in cash and cash equivalents. The Company raised $8.1 million during the second quarter through issuing of common stock through its ATM facility.
Operating expense for the second quarter of 2021 was $3.5 million, compared to $3.0 million in the second quarter of 2020.
R&D expense for the second quarter of 2021 was $3.2 million, compared to $2.5 million in the second quarter of 2020.
Net cash used in operating activities for the second quarter of 2021 was $6.8 million, compared to $6.3 million for the second quarter of 2020.
The net loss for the second quarter of 2021 was $7.2 million, compared to a net loss of $6.8 million in the second quarter of 2020. The basic and diluted loss per share was $0.13 in the second quarter of 2021, compared to a basic and diluted loss per share of $0.17 in the second quarter of 2020.
Anticipated Milestones and Catalysts

Dosing of the first patient in phase 1/2 GOBLET study in gastrointestinal cancer: H2 2021
Final biomarker data for AWARE-1 breast cancer study in the intended target population for a registrational study: H2 2021
Completion of enrollment in phase 2 BRACELET-1 metastatic breast cancer study: Q4 2021
Interim safety update from phase 2 IRENE study in triple-negative breast cancer: Q4 2021*
Interim safety data from phase 1 WINSHIP 4398-18 multiple myeloma study: Q4 2021*
*Guidance provided by clinical investigators

Oncolytics expects to provide updates on the timing of the following milestones:

Interim safety update from BRACELET-1 metastatic breast cancer study
Phase 2 BRACELET-1 metastatic breast cancer study: final data
Webcast and Conference Call

Management will host a conference call for analysts and institutional investors at 8:00 a.m. ET today, August 6, 2021. To access the call, please dial (888) 664-6383 (North America) or (416) 764-8650 (International) and, if needed, provide confirmation number 5114-8191. A live webcast of the call will also be available by clicking here or on the Investor Relations page of Oncolytics’ website (LINK) and will be archived for three months. A dial-in replay will be available for one week and can be accessed by dialing (888) 390-0541 (North America) or (416) 764-8677 (International) and using reference code: 148-191#.

About AWARE-1

AWARE-1 is an open label window-of-opportunity study in early-stage breast cancer enrolling 38 patients into five cohorts:

Cohort 1 (n=10), HR+ / HER2- (pelareorep + letrozole)
Cohort 2 (n=10), HR+ / HER2- (pelareorep + letrozole + atezolizumab)
Cohort 3 (n=6), TNBC (pelareorep + atezolizumab)
Cohort 4 (n=6), HR+ / HER2+ (pelareorep + trastuzumab + atezolizumab)
Cohort 5 (n=6), HR- / HER2+ (pelareorep + trastuzumab + atezolizumab)
The study combines pelareorep, without or with atezolizumab, and the standard of care therapy according to breast cancer subtype. Tumor tissue is collected from patients as part of their initial breast cancer diagnosis, again on day three following initial treatment, and finally at three weeks following treatment, on the day of their mastectomy. Data generated from this study are intended to confirm that pelareorep is acting as a novel immunotherapy, to evaluate potential synergy between pelareorep and checkpoint blockade, and to provide comprehensive biomarker data by breast cancer subtype. The primary endpoint of the study is overall CelTIL score (a measurement of cellularity and tumor-infiltrating lymphocytes). Secondary endpoints for the study include CelTIL by breast cancer subtype, safety, and tumor and blood-based biomarkers.

For more information about the AWARE-1 study, refer to View Source

Tecentriq (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group.

About BRACELET-1

The BRACELET-1(BReast cAnCEr with the Oncolytic Reovirus PeLareorEp in CombinaTion with anti- PD-L1 and Paclitaxel) study is an open-label, phase 2, randomized study in patients with HR+/HER2-, endocrine-refractory metastatic breast cancer being conducted under a co-development agreement with Merck KGaA, Darmstadt, Germany and Pfizer. PrECOG LLC, a leading cancer research network, is managing the study. The study will take place at 20 trial sites and is expected to enroll 45 patients randomized into three cohorts. A three-patient safety run-in was conducted with patients receiving pelareorep, paclitaxel, and avelumab prior to randomization. The three cohorts being treated are as follows:

Cohort 1 (n=15): paclitaxel
Cohort 2 (n=15): paclitaxel + pelareorep
Cohort 3 (n=18): paclitaxel + pelareorep + avelumab (Bavencio)
Patients in cohort 1 will receive paclitaxel on days 1, 8, and 15 of a 28-day cycle. Patients in cohort 2 will receive the same paclitaxel regimen as cohort 1, plus pelareorep on days 1, 2, 8, 9, 15 and 16 of the 28-day cycle. Patients in cohort 3 will receive the same combination and dosing regimen as cohort 2, plus avelumab on days 3 and 17 of the 28-day cycle. The primary endpoint of the study is overall response rate. Exploratory endpoints include peripheral and tumor T cell clonality, inflammatory markers, and safety and tolerability assessments.

For more information about the BRACELET-1 study, refer to View Source

About GOBLET

The GOBLET (Gastrointestinal tumOrs exploring the treatment comBinations with the oncolytic reovirus peLarEorep and anTi-PD-L1) study is a phase 1/2 multiple indication biomarker, safety, and efficacy study in advanced or metastatic gastrointestinal tumors. The study will be conducted at 15 centers in Germany. The primary endpoint of the study is safety, with overall response rate and biomarker evaluation (T cell clonality and CEACAM6) as exploratory endpoints. Approximately 55 patients are planned to be enrolled in four independent cohorts:

Pelareorep in combination with atezolizumab, gemcitabine, and nab-paclitaxel in 1st line metastatic pancreatic cancer patients (n=12);
Pelareorep in combination with atezolizumab in 1st line MSI (microsatellite instability)-high metastatic colorectal cancer patients(n=19);
Pelareorep in combination with atezolizumab and TAS-102 in 3rd line metastatic colorectal cancer patients (n=14); and
Pelareorep in combination with atezolizumab in 2nd line advanced and unresectable anal cancer patients (n=10).