On January 11, 2016 Advanced Accelerator Applications S.A. (NASDAQ:AAAP) ("AAA" or "the Company"), an international specialist in molecular nuclear medicine, reported an exclusive license agreement with Johns Hopkins University in Baltimore, Maryland to develop and market PSMA-SR6, a receptor ligand of Prostate-Specific Membrane Antigen (PSMA) for clinical therapeutic and diagnostic purposes (Press release, Johns Hopkins University, JAN 11, 2016, View Source [SID1234524452]). AAA will focus on developing this treatment and its companion diagnostic for prostate cancer through novel molecular nuclear medicine techniques similar to those implemented for the development of Lutathera and Somakit. Prostate cancer affects nearly 1 in 7 men during their lifetime worldwide.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The terms of the agreement include payment to Johns Hopkins of an upfront licensing fee, as well as certain milestone and royalty payments.

"This licensing agreement is the first step toward broadening our development pipeline by leveraging a formula that we have already successfully applied to develop our lead therapeutic and diagnostic candidates Lutathera and Somakit. We plan to radiolabel PSMA-SR6, to develop a 177Lu-PSMA-SR6 to treat and monitor prostate cancer and a 68Ga-PSMA-SR6, which will help to diagnose and stage disease. The PSMA expression pathway has been widely investigated with labelled antibodies, but we believe that a small molecule, with very high specificity and rapid uptake into tumors and clearance from non-targeted organs could be the ideal candidate for a full theragnostic approach. We are very pleased to partner with the Johns Hopkins University as they have been pioneering and leading this new field for many years," says Stefano Buono, Chief Executive Officer of AAA.

"Our license agreement with AAA extends Johns Hopkins University’s research leadership in PSMA to benefit patients," says Neil Veloso, Executive Director of Johns Hopkins Technology Ventures. "We are very pleased that AAA has selected PSMA-SR6 for full development for commercial applications in an area of significant patient need."

AAA is planning to support a proof-of-concept study in humans that may start in 2016 for both diagnostic and therapeutic applications of PSMA-SR6.

PSMA-SR6 is a unique second-generation selective prostate cancer PSMA receptor ligand developed by Dr Martin Pomper at Johns Hopkins University. PSMA-SR6 has a unique structure and is selective for PSMA expressed on prostate cancer tumor cells. It belongs to a new class of PSMA receptor ligands with high potential as diagnostic and therapeutic markers for prostate cancer. Studies have consistently demonstrated PSMA expression in all types of prostate tissue and an increased PSMA expression in cancer tissue.

On January 8, 2016 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, reported its 2016 business outlook (Filing, 8-K, Advaxis, JAN 11, 2016, View Source [SID:1234508767]). The outlook is intended to provide Advaxis investors with an overview of anticipated events and key milestones for the coming year.

Advaxis made significant strides in its clinical development programs in 2015. Positive data was presented at the 2015 American Gynecological & Obstetrical Society Annual Meeting from a Phase 2 study of lead compound axalimogene filolisbac in metastatic cervical cancer patients (GOG 0265). Axalimogene filolisbac exceeded historical survival rates in a refractory and heterogeneous patient population and, on the basis of this data, allowed the study to move forward into stage two. Advaxis commenced dosing of a Phase 1/2 trial of axalimogene filolisbac in combination with MedImmune’s durvalumab (anti-PD-L1 immune checkpoint inhibitor) for metastatic cervical cancer and head and neck cancer. The Company also began dosing of a Phase 1/2 trial of ADXS-PSA in combination with Merck’s Keytruda (pembrolizumab; anti-PD-1 immune checkpoint inhibitor) for metastatic prostate cancer. A third product candidate, ADXS-HER2, targeting HER2 positive cancers, moved into the clinic and commenced dosing.

Advaxis made significant progress in its business operations, including raising more than $100M in capital. Presented with the challenge of a clinical hold on all of its programs, Advaxis worked closely with the U.S. Food and Drug Administration (FDA) to have the hold lifted in a timely manner.

2016 OPERATIONAL MILESTONES

Advaxis anticipates the following operational milestones in 2016:

Clinical Operations

Axalimogene Filolisbac

● Finish the Special Protocol Assessment (SPA) process and initiate enrollment in a Phase 3 trial for the treatment of high-risk, locally advanced cervical cancer (AIM2CERV) in mid-2016.

● Complete enrollment of stage 2 of GOG 0265 study in patients with metastatic cervical cancer in 2016.

● Initiate Phase 2 study in combination with Incyte’s epacadostat (IDO-1 inhibitor) for the treatment of early stage cervical cancer in the first half of 2016.

● Commence enrollment of Phase 2 trial in metastatic anal cancer (FAWCETT) in the first half of 2016.

● Complete enrollment in the combination Phase 1/2 study with MedImmune’s durvalumab (anti-PD-L1 immune checkpoint inhibitor) for the treatment of HPV-associated head and neck and cervical cancer in late 2016.

● Following the successful completion of cohort 1 of the combination, which occurred in 2015, fully enroll cohort 2 (with a higher dose of durvalumab).

● Following completion of cohort 2, a dose determination will be made and enrollment in the expansion phase of the study will commence in the first half of 2016, with completion of enrollment by the end of 2016.

● Commence and complete enrollment of the Phase 2 dose-escalation study in recurrent cervical cancer (at 1×1010 cfu) in the first half of 2016.

● Present data from a Phase 1/2 window of opportunity trial in HPV-positive head and neck cancer in the first half of 2016 at a major medical meeting.

● Commence enrollment of Phase 2 study in patients with HPV-positive, non-squamous, non-small cell lung cancer following first-line induction chemotherapy via partner in the first half of 2016.

● Commence investigator initiated studies, including for other HPV-associated cancers (e.g., penile and vaginal cancers).

ADXS-PSA

● Complete enrollment of Phase 1/2 study in combination with Merck’s Keytruda (pembrolizumab), an anti-PD-1 immune checkpoint inhibitor, for the treatment of advanced, metastatic castrate-resistant prostate cancer.

● Following the successful completion of dose escalation cohorts 1 and 2, which occurred in 2015, fully enroll cohort 3 (highest dose at 1×1010) in the first half of 2016.

● Once a dose determination is made, enrollment in the Part B combination arm with ADXS-PSA and Keytruda will commence in the first half of 2016, with completion of enrollment by the end of 2016.

ADXS-HER2

● Complete enrollment of Phase 1b dose-escalation study of ADXS-HER2 in patients with HER2-driven malignancies in the first half of 2016.

● Fully enroll Part A, which is designed to establish safe dosing levels in preparation for the expansion phase of the study in HER2-driven malignancies.

● Once a dose is selected from Part A, enrollment in a Part B expansion phase will commence in the second half of 2016.

● Following completion of Part A in the Phase 1b dose escalating study, commence collaboration and cooperative group trial with the Children’s Oncology Group in osteosarcoma.

● Initiate commercialization via Aratana Therapeutics (NASDAQ:PETX) (using the name AT-014) for the treatment of canine osteosarcoma following approval from the U.S. Department of Agriculture (USDA).

Expanding Pipeline

ADXS-NEO

● MINE (My Immunotherapy Neo-Epitopes), a collaboration with Memorial Sloan Kettering Cancer Center, will progress toward the filing of an IND in 2016. MINE uses Advaxis’s Lm Technology to develop neoepitope immunotherapies based on an individual patient’s tumor.

ADXS-TNBC

● Preclinical work will be finalized for ADXS-TNBC, a multiple-antigen construct for Triple Negative Breast Cancer (TNBC) with the goal of filing an IND in 2016.

Enhanced Manufacturing Capabilities

● Advaxis will continue to enhance its internal process/analytical development, quality systems, manufacturing and quality control infrastructure with the goal of accelerating and advancing its pipeline. The company plans to broaden its capabilities through the completion of a new pilot plant, GMP manufacturing facility, research and development labs, and quality control labs. In addition, Advaxis plans to undertake several technology transfers with its partners and install new innovative technologies to reduce lead times and to improve the overall supply chain.

Business Development

● Advaxis will continue to pursue partnerships for its cancer immunotherapy platform to enable additional research in combination with other cancer therapies and novel immunotherapies.

● Advaxis also continues to explore options for retaining a Latin American partner for axalimogene filolisbac to collaborate on co-development and registration in this important region.

SECOND HALF 2015 REVIEW

Since issuing its first half 2015 business update in June, Advaxis achieved several regulatory, clinical, business and operational milestones during the second half of 2015.

Clinical Milestones

Axalimogene Filolisbac

● August 20: Advaxis and MedImmune commenced enrollment in Phase 1/2 trial. First patient was enrolled in a Phase 1/2 study of axalimogene filolisbac in combination with MedImmune’s investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736), for the treatment of patients with advanced, recurrent or refractory HPV-associated cervical cancer and HPV-associated head and neck cancer.

● September 14: U.S. Food and Drug Administration’s (FDA) Office of Orphan Products Development awarded a three-year $1.1 million grant to Baylor College of Medicine for an ongoing Phase 2 trial in HPV-associated oropharynx (throat) cancer.

● September 17: Data from stage 1 of Phase 2 Study (GOG-0265) of ADXS-HPV were presented at 2015 American Gynecological & Obstetrical Society Annual Meeting. In patients with persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRMCC), who have progressed on at least one prior line of systemic therapy, treatment with axalimogene filolisbac resulted in a 38.5 percent 12-month overall survival rate in 26 patients.

● November 9: Poster at the Society for Immunotherapy Cancer annual meeting showed that axalimogene filolisbac may be safely administered with prophylactic antibiotics up to 1 x 1×1010 cfu in patients with PRMCC, a tenfold increase from prior studies.

● December 14: Advaxis receives Orphan Drug Status from the European Medicines Agency for axalimogene filolisbac for the treatment of anal cancer.

ADXS-PSA

● August 5: Movember Foundation and Prostate Cancer Foundation each awarded grants of $1 million to two research projects in metastatic, treatment-resistant prostate cancer.

ADXS-HER2

● September 28: First patient treated in Phase 1b dose-escalation study of Advaxis’s ADXS-HER2 in HER2-expressing solid tumors. The study is the first in-human study of the Lm Technology immunotherapy product for HER2 expressing cancers.

● December 1: Company receives Orphan Drug Status from the European Medicines Agency for axalimogene filolisbac for the treatment of anal cancer.

Business & Operations

Advaxis achieved the following operational milestones in the second half of 2015:

● The company significantly expanded its IP portfolio of new products including ADXS-NEO (neoepitopes) and PSA-2.0. In addition, Advaxis down-scaled its manufacturing process to enable rapid turn-around of ADXS-NEO for clinical use.

● Over the course of 2015, Advaxis expanded its leadership team, deepening its medical, clinical operations, manufacturing and regulatory affairs functions:

● Mayo Pujols, Vice President, Manufacturing

● Thomas W. Hare, Vice President, Clinical Operations

● Bob Ashworth, Vice President, Regulatory Affairs

● June 29: Daniel J. O’Connor received the 2015 Ernst & Young New Jersey Entrepreneur of the Year award.

● July 21: Advaxis received two patents from the United States Patent and Trademark Office (USPTO) of patents with composition of matter claims for ADXS-PSA and methods of use claims for ADXS-HER2.

● August 13: Advaxis appointed Tom Ridge, first Secretary of Homeland Security and 43rd Governor of Pennsylvania, to its board of directors.

● August 26: Advaxis announced a $25M licensing agreement with Knight Therapeutics to help commercialize its three lead drug candidates in Canada.

● September 10: Advaxis was the inaugural recipient of the Medical Visionary Angel Award from the Farrah Fawcett Foundation.

● October 27: Launched Research Collaboration with Memorial Sloan Kettering Cancer Center to develop neo-epitope immunotherapies based on an individual patient’s tumor (MINE).

● November 17: Received $1.6M Tax Credit from New Jersey Technology Business Tax Program.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On January 11, 2016 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing novel protein therapeutics for cancer and inflammatory diseases, reported an update on GlaxoSmithKline’s (GSK) ongoing Phase 1b clinical trial of FP-1039/GSK3052230, an FGF ligand trap, in patients with squamous non-small cell lung cancer (sqNSCLC) and mesothelioma (Press release, Five Prime Therapeutics, JAN 11, 2016, View Source [SID:1234508729]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

GSK presented preliminary clinical safety and efficacy data from the Phase 1b trial at the World Conference on Lung Cancer on September 9, 2015. At the time, data from Arm A in treatment-naïve sqNSCLC patients were encouraging, Arm B in second line sqNSCLC had few patients enrolled, and data from Arm C were immature because few mesothelioma patients were then evaluable. Based on preliminary data, GSK and Five Prime have agreed to continue to enroll up to 30 mesothelioma patients at the expansion dose of 15 mg/kg in Arm C of the trial. GSK plans to submit data for presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Annual Meeting in June. The companies have also agreed to stop enrolling the sqNSCLC patient study cohorts given the change in treatment paradigms following approvals of immuno-oncology agents and the increasingly competitive landscape.

"We are encouraged by the preliminary data we have recently reviewed from the mesothelioma arm of the study and look forward to seeing the results as additional patients are enrolled and followed," said Lewis T. "Rusty" Williams, M.D., Ph.D., president and chief executive officer of Five Prime. "The majority of mesothelioma tumors express high levels of FGF-2, so our FGF ligand trap represents a rational therapeutic approach, and patients currently have limited treatment options. If we see similar results once we have full, mature data for Arm C, we will seek to regain rights for FP-1039 in the U.S., Canada and the E.U. from GSK, as mesothelioma could represent a potentially attractive market opportunity for Five Prime."

About the Phase 1b Trial

The Phase 1b clinical trial of FP-1039 is being conducted by GSK and is designed as a three-arm, multicenter, non-randomized, parallel-group, uncontrolled, open-label trial. This clinical trial was designed to evaluate the safety, tolerability, dosage, response rate and duration of response of FP-1039:

in combination with paclitaxel and carboplatin in previously untreated metastatic sqNSCLC (Arm A);
in combination with docetaxel in metastatic sqNSCLC that has progressed after previous therapy (Arm B); or
in combination with front-line pemetrexed and cisplatin in mesothelioma (Arm C), a tumor in which the FGF-2 ligand is overexpressed.

About FP-1039

FP-1039 is a protein drug designed to intervene in FGF signaling. As a ligand trap, FP-1039 binds to FGF ligands circulating in the extracellular space (such as FGF-2), preventing these signaling proteins from reaching FGFR1 on the surface of tumor cells where they would otherwise stimulate cancer cell division and/or angiogenesis. However, FP-1039 does not bind to certain "hormonal" FGFs, including FGF-23, which regulates phosphate levels in the blood. As a result, treatment with FP-1039 treatment has not been shown to cause hyperphosphatemia, a side effect seen with small molecule inhibitors of FGF receptors, which block the activity of both cancer-associated FGFs and FGF-23.

About Mesothelioma

Mesothelioma is a disease with high unmet medical need and high mortality rate. A majority of mesothelioma patients have tumors with abnormally high levels of FGF-2. In preclinical testing, Five Prime observed inhibition of mesothelioma tumor growth with single-agent FP-1039. Mesothelioma is an orphan indication in the United States with a prevalence of about 4,000 patients and incidence of about 3,000 patients. Worldwide, there are a total of approximately 14,000 cases of mesothelioma diagnosed each year.

On January 11, 2016 Ionis Pharmaceuticals, Inc. (NASDAQ: IONS) reported that the Company expects to significantly improve upon its financial guidance for 2015 (Press release, Isis Pharmaceuticals, JAN 11, 2016, View Source;p=RssLanding&cat=news&id=2128373 [SID:1234508772]). The Company expects to end 2015 with a pro forma net operating loss (NOL) in the low $20 million range and more than $775 million in cash.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Over the past several years, we have created a strong and consistent financial foundation. Our corporate partnerships have produced increasing levels of revenue as our partnered programs have matured and expanded. We have been able to support the advancement of our very large pipeline with modest expense growth due to the efficiency of our technology platform as well as the significant in-kind contributions of our partners. With three potentially transformational medicines close to commercialization, we look forward to adding product revenues and royalties to our revenue base over the next few years," said Elizabeth L. Hougen, chief financial officer of Ionis Pharmaceuticals. "We expect to end 2015 with a pro forma NOL in the low $20 million range, which represents a 60% improvement over our original guidance. In addition, we expect to end 2015 with more than $775 million in cash, substantially exceeding our 2014 year-end cash balance and our 2015 cash guidance. Importantly, our significant increase in revenue over the last several years reflects the successes in all of our collaborations as the drugs in those collaborations advanced."

The Company intends to provide financial guidance for 2016 in connection with its year-end 2015 financial results in February.

Pipeline Update
Ionis management will present an update today on its drug development pipeline at the J.P. Morgan conference, including an update on its ongoing open-label Phase 2 clinical study of nusinersen in infants with Type I spinal muscular atrophy (SMA). Previously the company reported data from this study on event-free survival, measures of muscle function and assessments of developmental milestones. The data reported today show continued increases in median event-free survival and muscle function scores. The safety and tolerability profile of nusinersen to date continues to support further development.

In 2015, Ionis added nine new drugs to its pipeline. Already in 2016, the company has added two new drugs to its pipeline: IONIS-BIIB5Rx and IONIS-BIIB6Rx. Both new drugs are being developed together with Biogen and are designed to address undisclosed targets for the treatment of patients with neurodegenerative diseases. Ionis currently has a total of 38 drugs in its pipeline.

"We believe we are just beginning to realize the value we have created. We have three potentially groundbreaking medicines for which we have completed target enrollment in the respective pivotal Phase 3 trials and preparations are underway for each of these drugs for the necessary regulatory filings for marketing authorization. In addition, we and our partners are well along in preparing to commercialize these medicines. As our pipeline continues to mature, we have many other medicines coming along behind these three late-stage drugs," said B. Lynne Parshall, chief operating officer at Ionis. "We have also demonstrated in 2015 that the advances we are making in our technology continue to make better and better medicines, which allows us to expand the application of our drugs to new tissues, new targets and new diseases. All of this sets us up for an exciting and event-filled 2016."

In January 2016, Ionis terminated its license agreement with Sanofi Genzyme for KYNAMRO (mipomersen sodium).

"We are disappointed that we have had to terminate our contract with Genzyme to commercialize KYNAMRO," said Ms. Parshall. "We know that KYNAMRO is an important drug for patients with homozygous FH. Genzyme is continuing to support patients and physicians as we explore other potential commercialization options."

In addition, Ionis announced that results from the Phase 1/2 study with IONIS-AR-2.5Rx in heavily pretreated, late-stage prostate cancer patients demonstrated encouraging data, including several durable reductions in PSA levels. The drug also exhibited a good safety and tolerability profile supportive of continued development. Data from this study will be presented later in the year. Ionis plans to continue the development of IONIS-AR-2.5Rx independent of AstraZeneca.

On January 11, 2016 AstraZeneca and Incyte Corporation reported a new collaboration to evaluate the efficacy and safety of Incyte’s Janus-associated kinase (JAK) 1 inhibitor, INCB39110, in combination with AstraZeneca’s next generation epidermal growth factor receptor (EGFR) inhibitor, Tagrisso (osimertinib) (Press release, AstraZeneca, JAN 11, 2016, View Source [SID:1234508733]). The combination will be assessed as a second line treatment for patients with EGFR mutation-positive non-small cell lung cancer (NSCLC), who have been treated with a first generation EGFR tyrosine kinase inhibitor (TKI) and subsequently developed the T790M resistance mutation.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

There is increasing evidence that signalling through the JAK-STAT (signal transducer and activator of transcription) pathway could be a contributing factor in resistance to EGFR TKI treatment in patients with EGFR mutation NSCLC. Blocking both JAK and EGFR activity may therefore offer an improved targeted treatment benefit in some patients.

Under the terms of the agreement, AstraZeneca and Incyte will collaborate on a Phase I/II study, to be conducted by Incyte. The Phase I part of the trial is expected to establish a recommended dose regimen for the combination of INCB39110 and Tagrisso, while the Phase II part of the study will assess the safety and efficacy profile. Results from the study will be used to determine whether further clinical development of this combination is warranted.

Antoine Yver, Head of Oncology, Global Medicines Development at AstraZeneca said: "We are pleased to be building on our existing relationship with Incyte and exploring a potentially exciting combination for lung cancer patients who have developed a resistance to first generation EGFR inhibitor treatment. This collaboration allows us to explore further ways in which Tagrisso, our first in class T790M-directed tyrosine kinase inhibitor, can help meet urgent unmet patient need, following its accelerated approval in the US and the recent positive CHMP opinion, recommending approval in Europe."

Rich Levy, MD, Chief Drug Development Officer of Incyte said: "The expansion of our research collaboration with AstraZeneca will allow us to further our understanding of these two compounds and explore their potential synergies which support our goal of delivering innovative medicines that will benefit patients with cancer or other diseases. We look forward to adding to our ongoing clinical research for INCB39110 and exploring the potential of this combination."

This agreement builds on an existing collaboration between the two companies, announced in May 2014, to explore AstraZeneca’s anti-PD-L1 immune checkpoint inhibitor, durvalumab, in combination with Incyte’s oral indoleamine dioxygenase-1 (IDO1) inhibitor, epacadostat (INCB24360).

NOTES TO EDITORS

About Tagrisso (osimertinib)

Tagrisso (osimertinib) is the only approved medicine indicated for adult patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer. This indication is approved under the FDA’s accelerated approval process based on tumour response rate and duration of response (DoR). Osimertinib is being compared with platinum-based doublet chemotherapy in the confirmatory AURA3 Phase III study in patients with EGFR T790M-positive, locally advanced, or metastatic NSCLC who have progressed after EGFR-TKI therapy. It is also being investigated in the adjuvant and metastatic first-line settings, including in patients with brain metastases, and in combination with other compounds.

Non-clinical in vitro studies have demonstrated that osimertinib has high potency and inhibitory activity against mutant EGFR phosphorylation across the range of clinically relevant EGFRm and T790M mutant NSCLC cell lines, with significantly less activity against EGFR in wild-type cell lines.

About INCB39110

INCB39110 is an orally bioavailable, isoform-selective inhibitor of Janus-associated kinase 1 (JAK1). JAK1 activity is believed to play an important role in both autoimmune and oncologic diseases. JAK1 forms heterodimeric complexes with JAK2, JAK3 or TYK2 and functions as an immunomodulatory and inflammatory signalling kinase. Selective JAK1 inhibition prevents STAT signalling downstream of a number of cytokines, including IL-6, IL-10 and interferon-gamma. Consistent with the dominant role for JAK1 in mediating heterodimeric JAK/STAT signalling, JAK1 inhibition has been shown to result in equivalent efficacy compared to balanced JAK1/JAK2 modulation in a variety of preclinical solid and liquid tumor models. INCB39110 will be investigated in clinical trials as monotherapy in graft versus host disease (GvHD) and in several combination-based therapeutic regimens, including with PI3Kδ (INCB50465), IDO1 (epacadostat) and EGFR (Tagrisso) inhibitors.