On July 17, 2018 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage biopharmaceutical company focused on creating innovative cancer immunotherapies, reported the final unblinded safety data from its Phase 1 trial for AB928, its dual adenosine receptor antagonist, in healthy volunteers (Press release, Arcus Biosciences, JUL 17, 2018, View Source [SID1234527745]). These results demonstrated that AB928 was safe and well tolerated at all doses evaluated. Pharmacokinetic and pharmacodynamic data from this trial were previously presented in April at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

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"We are pleased to see that AB928 was safe and well tolerated in healthy volunteers, even at 200 mg once-daily, the highest dose tested in the study. In addition, pharmacodynamic data from this trial demonstrated that an AB928 dose between 75 mg and 150 mg once-daily should be sufficient to achieve greater than 90% inhibition of the adenosine 2a (A2a) receptor pathway," said Joyson Karakunnel, MD, MSc, FACP, Vice President of Clinical Development at Arcus. "These results demonstrate that AB928 has an attractive profile to be combined with standard-of-care regimens for the treatment of cancer, such as anti-PD-1 antibodies or chemotherapy, particularly in settings where adenosine is believed to play an immuno-suppressive role. The results also support the selection of the starting dose for the combination of AB928 and AB122, our anti-PD-1 antibody, in patients."

Design of the Phase 1 Trial for AB928 in Healthy Volunteers

The Phase 1 double-blinded, randomized, placebo-controlled trial enrolled 85 healthy volunteers. The trial included a single-ascending-dose (SAD) portion and a multiple-ascending-dose (MAD) portion. In the SAD portion, single doses of 10, 25, 75 and 150 mg and a twice-daily dose of 100 mg were evaluated. In the MAD portion, once-daily doses of 10, 25, 75 and 150 mg and 200 mg (with food) were administered to subjects for four consecutive days. In each dosing cohort, six subjects received AB928 and two subjects received placebo.

Summary of the Phase 1 Safety Results

All reported adverse events (AEs) were characterized as low-grade AEs (Grade 1 or Grade 2), with the majority of the AEs being Grade 1 events.
No AEs appeared to be dose dependent, and no AEs prevented escalation to a higher dose.
All treatment-related AEs were resolved by the end of the study period, and no serious adverse events, discontinuations or deaths were reported in the study.
There were no variations in heart rate or blood pressure that would not be considered within normal parameters.
Based on the results from the healthy-volunteer trial, patients in the first dose-escalation cohort for the Phase 1/1b program, which will evaluate AB928 + AB122, will receive once-daily doses of 75 mg of AB928. The Company plans to present the final safety results from the Phase 1 healthy-volunteer trial at a medical conference later in the year.

About the Phase 1/1b Program for AB928

The Phase 1/1b program for AB928 is designed to evaluate the safety and clinical activity of the combinations of AB928 + AB122 and AB928 + chemotherapy in selected tumor types characterized by high levels of adenosine and / or CD73 as well as T cell infiltration. These tumor types include triple negative breast cancer, ovarian cancer, colorectal cancer, gastroesophageal cancer, non-small cell lung cancer and renal cell carcinoma. As part of the Phase 1/1b program, the Company also expects to evaluate the triple combination of AB928 + anti-PD-1 therapy + chemotherapy in certain settings such as non-small cell lung cancer. The Company plans to present dose-escalation data for the combinations, including data on safety, biomarker analysis and clinical activity, in the first half of 2019.

About AB928

AB928 is an orally bioavailable, highly potent antagonist of the adenosine 2a and 2b receptors. The activation of these receptors by adenosine interferes with the activity of key populations of immune cells and inhibits an optimal anti-tumor immune response. By blocking these receptors, AB928 has the potential to reverse adenosine-induced immune suppression within the tumor microenvironment. AB928 was designed specifically for the oncology setting, with a profile that includes potent activity in the presence of high concentrations of adenosine and a minimal shift in potency due to non-specific protein binding, both essential properties for efficacy in the tumor microenvironment. AB928 has other attractive features, including high penetration of tumor tissue and low penetration through the healthy blood-brain barrier. In a Phase 1 trial in healthy volunteers, AB928 has been shown to be safe and well tolerated and to have pharmacokinetic and pharmacodynamic profiles consistent with a once-daily dosing regimen.

About AB122

AB122 is a fully human IgG4 antibody that potently and selectively blocks PD-1. The biochemical, biological and preclinical properties of AB122 have been shown to be similar to those of the marketed anti-PD-1 antibodies nivolumab and pembrolizumab. In August 2017, Arcus entered into a license agreement with WuXi Biologics for an exclusive license to develop, use, manufacture, and commercialize AB122 worldwide except for China and five other countries outside of the U.S., Europe, Japan. In November 2017, dosing was initiated in Australia for the Phase 1 trial of AB122 in cancer patients. The Company plans to report initial data from this trial in the third quarter of 2018. The Company expects AB122 to form the backbone of many of its intra-portfolio combinations.

On July 17, 2018 Vanda Pharmaceuticals Inc. (Vanda) (NASDAQ: VNDA) reported it will release results for the second quarter of 2018 on Wednesday, August 1, 2018, after the market closes (Press release, Vanda Pharmaceuticals, JUL 17, 2018, View Source [SID1234527746]).

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Vanda will host a conference call at 4:30 PM ET on Wednesday, August 1, 2018, during which management will discuss the second quarter 2018 financial results and other corporate activities. To participate in the conference call, please dial 1-800-708-4539 (domestic) or 1-847-619-6396 (international) and use passcode 47289344.

The conference call will be broadcast simultaneously and archived on Vanda’s website, www.vandapharma.com. Investors should go to the website at least 15 minutes early to register, download, and install any necessary audio software.

A replay of the call will be available on Wednesday, August 1, 2018, beginning at 7:00 PM ET and will be accessible until Wednesday, August 8, 2018, at 11:59 PM ET. The replay call-in number is 1-888-843-7419 for domestic callers and 1-630-652-3042 for international callers. The passcode number is 47289344.

On July 17, 2018 Inflection Biosciences Ltd, a private company developing innovative therapeutics for cancer, reported the publication of preclinical data showing the company’s dual mechanism PIM/PI3 kinase inhibitor IBL-202 has promise as a treatment for chronic lymphocytic leukaemia (CLL) (Press release, Inflection Biosciences, JUL 17, 2018, View Source [SID1234527747]). This research has been published in the most recent issue of the peer-reviewed British Journal of Haematology.

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The preclinical research was conducted in collaboration with Dr. Oliver Giles Best of the Northern Blood Research Centre, Kolling Institute of Medical Research, University of Sydney, Australia, and a member of the CLL Australian Research Consortium (CLLARC), Sydney, Australia.

Despite significant advances in treatment, CLL remains an incurable disease. Given the growing body of evidence suggesting CLL cells may adapt to, survive and even proliferate under hypoxic conditions of the tumour microenvironment, new treatment options which are effective under these conditions are required.

These published results show that IBL‐202 is cytotoxic against CLL cells under in vitro conditions that mimic the hypoxic tumour microenvironment. The publication also demonstrates the significant effects of IBL‐202 on CD49d and CXCR4 gene expression and on the migration, cycling and proliferation of CLL cells, suggesting the drug may significantly impair the migratory and proliferative capacity of the leukaemic cells.

Dr. Best, lead author on the publication, commented: "Collectively, this data demonstrates that dual inhibition of the PIM and PI3 kinases by IBL‐202 may be an effective strategy for targeting CLL cells, particularly within the environmental niches known to confer drug‐resistance."

The complete article titled ‘The dual inhibitor of the phosphoinositol‐3 and PIM kinases, IBL‐202, is effective against chronic lymphocytic leukaemia cells under conditions that mimic the hypoxic tumour microenvironment’ can be accessed here.

On July 16, 2018 Idera Pharmaceuticals, Inc. (NASDAQ:IDRA), a pharmaceutical company focused on the development and commercialization of its proprietary immune modulator, tilsotolimod, for the treatment of cancer, is reported the company’s corporate strategy and outlook following the recent termination of its proposed merger with BioCryst Pharmaceuticals (Press release, Idera Pharmaceuticals, JUL 16, 2018, View Source [SID1234527721]).

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Vincent Milano, Idera’s Chief Executive Officer stated, "Today, we advance the next chapter of our company’s future with a clear picture of our mission, which is to ultimately deliver tilsotolimod to as many patients suffering from cancer as we possibly can. We have generated a significant body of evidence for tilsotolimod, including pre-clinical studies, translational research and meaningful clinical data in our ongoing ILLUMINATE-204 trial in anti-PD-1 refractory melanoma, as well as Fast Track Designation from the Food and Drug Administration. This gives us a great deal of confidence in tilsotolimod’s ability to prime the immune system to play a more powerful role in the fight against cancer, representing an exciting value proposition for both shareholders and patients."

Milano continued, "We are executing on the pivotal Phase 3 trial, ILLUMINATE-301, in anti-PD-1 refractory melanoma and are partnering with three separate planned investigators/institutions in support of their respective investigator sponsored trials (ISTs), each of which is exploring tilsotolimod in different patient populations. Through the body of data we’ve generated to date, as well as from our discussions with our key opinion leader advisors, it has become abundantly clear to us that tilsotolimod has the opportunity to play a more expanded role in the immuno-oncology landscape, particularly in tumor types with limited immunogenicity that have not previously responded well to check-point inhibition approaches."

Financial Outlook and Other Corporate Updates

Idera ended the 1st Quarter of 2018, with cash and cash equivalents totaling $107.5 million, which as of the reporting of the first quarter of 2018 is anticipated to fund current operations into the third quarter of 2019. Subsequently, Idera announced an agreement with Bristol-Myers Squibb related to the funding of ipilimumab for the ILLUMINATE-301 trial, the cost of which we had previously budgeted for in our cash forecast, and as a result of the terminated merger with BioCryst Pharmaceuticals we also received $6 million in related fees. These two items have not yet been reflected in the Company’s financial runway and will be updated as the results of the 2nd quarter of 2018 are reported.

In addition, as previously disclosed on June 20, 2018, shareholders voted to approve giving the Board of Directors discretion to implement a reverse stock split of not less than 1-for-4 and not more than 1-for-8.

Idera has Significant Near-term Milestones Representing Substantial Value Creation Opportunities:

• Continued updates on ILLUMINATE-204 Phase 2 trial of tilsotolimod in combination with ipilimumab in patients with PD-1 refractory melanoma at upcoming medical conferences;

Recently increased trial sites open to enrollment to 7, (3 additional planned);
Expected completion of enrollment (N=60 patients) by year end 2018;
• Data update following completion of ILLUMINATE-204 Pembrolizumab combination Phase 1 component of the trial;

• Data from ILLUMINATE-101 tilsotolimod monotherapy trial;

• Complete enrollment in ILLUMINATE-204 with topline data in mid-2019;

• Initiation of Investigator Sponsored Trials (IST):

A Phase 1/2 open label study of intratumoral tilsotolimod in combination with intratumoral ipilimumab and IV nivolumab in a protocol open to multiple tumor types including non-small cell lung cancer (NSCLC), melanoma, squamous cell carcinoma of the head and neck and urothelial carcinoma. The principal investigator initiating this trial is Aurélien Marabelle, MD, PhD, Clinical Director of the Cancer Immunotherapy Program at Institut Gustave Roussy, Villejuif, France.
A Phase 2 study of intratumoral tilsotolimod in combination with IV pembrolizumab in patients with NSCLC. The principal investigator initiating this trial is Arafat Tfayli, MD, Professor of Clinical Medicine, Director of Hematology/Oncology Fellowship Program at the American University of Beirut Medical Center (AUBMC), Lebanon.
A Phase 2 placebo controlled study of intradermal administration of tilsotolimod in patients with T3/T4 primary melanoma scheduled to undergo a combined re-excision and sentinel node biopsy (SNB) procedure. The principal investigators initiating this are Bas Koster, MD and Tanja de Gruijl, PhD at The VU University Medical Center, Amsterdam, the Netherlands, and
• Potential collaborations and or partnerships with immuno-oncology companies to further demonstrate the utility of tilsotolimod in treating solid tumors.

About Tilsotolimod (IMO-2125)
Tilsotolimod is a TLR 9 agonist that received Fast Track Designation from the US Food and Drug Administration (FDA) in 2017 for the treatment of anti-PD-1 refractory melanoma, in combination with ipilimumab as well as orphan drug designation from the FDA for the treatment of melanoma Stages IIb to IV. It signals the immune system to create and activate cancer-fighting cells (T-cells) to target solid tumors. Currently approved immuno-oncology treatments, specifically check-point inhibitors, work for some but not all, as many patients’ immune response is missing or weak and thus they do not benefit from the checkpoint therapy. Intratumoral injections with tilsotolimod are designed to selectively enable the T-cells to recognize and attack cancers that remained elusive and unrecognized by the immune system exposed to checkpoint inhibitors alone, while limiting toxicity or impact on healthy cells in the body.

Out of the 30 patients treated and evaluated across all four dosing cohorts from the beginning of the Phase 1 portion of the study through our presentation at ASCO (Free ASCO Whitepaper) 2018, in the ILLUMINATE-204 Phase 1/2 Ipilimumab combination arm, 9 patients have RECIST v1.1 responses (PR or CR) representing a 30% Overall Response Rate (ORR). Based on the combination of clinical responses and supportive translational evidence, the 8mg dose of tilsotolimod was selected for clinical development advancement in the anti-PD-1 refractory melanoma indication.

Key findings from the most recent data presented at ASCO (Free ASCO Whitepaper) in June 2018 related to the ILLUMINATE-204 Phase 2 trial assessing the combination of the 8mg dose of tilsotolimod in combination with ipilimumab in anti-PD-1 refractory metastatic melanoma included:

21 patients treated with the 8mg dose of tilsotolimod in combination with ipilimumab have had disease evaluations (as of May 9, 2018 data cut);
RECIST v1.1 responses (including 2 Complete Response [CR]) were observed in 8 of these 21 patients (38.1%);
Six of 8 responses are ongoing (1 CR ongoing for nearly 2 years); median duration of response has not yet been reached;
Overall 15 out of these 21 patients (71.4%) experienced disease control (CR, PR, or SD);
The combination regimen is generally well tolerated. 6 of 26 patients (23%) had immune-related toxicities indicating that tilsotolimod + ipilimumab does not appear to add toxicity versus treatment with ipilimumab alone.
Injection-related toxicities were grade 1-2 transient fever and flu-like symptoms lasting <48 hours; and,
15 of 26 patients (57.7%) with lesions accessible only by image-guided injection (5 deep visceral lesions and 10 lymph nodes) were included.

On July 16, 2019 MaxCyte reported that it has received Investigational New Drug (IND) clearance from the US Food and Drug Administration (FDA) to begin a clinical study in the United States with its first wholly-owned chimeric antigen receptor (CAR) therapeutic candidate, MCY-M11 (Press release, MaxCyte, JUL 16, 2018, View Source [SID1234537625]).

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"The IND clearance marks an important milestone for MaxCyte. We are excited to advance MCY-M11, our first therapeutic candidate in solid tumors into the clinic and we hope that the upcoming study will serve as validation of our proprietary CARMA (CAR therapeutic) drug platform as a whole," said MaxCyte CEO Doug Doerfler. "This initial study will help determine the safety and potential effectiveness of the CARMA platform, and if successful, will mark its place as a new autologous cell-therapy platform for developing improved targeted cell-based immune therapies."

The IND allows for a Phase I clinical study to evaluate the safety of MCY-M11 in individuals with relapsed/refractory ovarian cancer and peritoneal mesothelioma. The clearance is for the Company’s first clinical study with MCY-M11, which is a drug candidate for next-generation CAR-engineered cell therapy. MCY-M11 is differentiated from traditional CAR therapies by its use of messenger RNA (mRNA) to engineer fresh peripheral blood mononuclear cells, allowing rapid manufacture and delivery back to the patient, without the need for a viral component or cell expansion. This cell therapy provides for transient expression, engineered with the potential to minimize the adverse side-effects seen in viral-based CAR therapies. MaxCyte anticipates commencing dosing of patients in H2 2018.

About the CARMA (CAR Therapy) Platform
CARMA is MaxCyte’s unique and proprietary CAR therapy platform in immuno-oncology. The platform is used to develop CAR therapies for a broad range of cancer indications. It offers the potential to deliver autologous cell therapies across a wide range of targets with a much quicker turnaround to the patient than traditional autologous cell therapies. More information on MaxCyte’s CARMA program is available at www.maxcyte.com/car/.