September 1, 2020

Impact: Moderate

  • Gilead has reached an exclusive licensing agreement for Jounce Therapeutic’s JTX-1811. JTX-1811 is a monoclonal antibody (mAb) that targets CCR8 to deplete immunosuppressive tumor-infiltrating T regulatory cells (Tregs). CCR8 is expressed by these Tregs and they are depleted by JTX-1811 treatment.
  • JTX-1811 has yet to enter the clinic, an IND is anticipated to be filed in the 1H2021.
  • Per terms of the agreement, Gilead will make an upfront payment of $85 million in addition to a $35 million equity investment ($120M total). Future milestone payments (clinical, regulatory, and/or commercial) have the potential to reach $685 million.
    • Jounce is also eligible to receive royalties ranging from the high single digit to mid-teens for worldwide sales.
  • Jounce will lead development of JTX-1811 through IND clearance, and after Gilead will have the sole right to develop JTX-1811.

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August 25, 2020

Impact: Moderate

Highlights

Immunovant reported topline results for its Phase 2a ASCEND-MG trial of IMVT-1401, an SC anti-FcRN, in MG:

  • Three arms were included (6 weeks treatment period with weekly dosing): 340 mg IMVT-1401 weekly (N=5), 680 mg IMVT-1401 weekly (N=5), and placebo (N=5). Targeted enrollment rate was 21 patients, but trial was unblinded at 15 patients to accelerate phase 3 program. Patients are currently completing the OLE. Full results will be shared at a future medical meeting.
  • IMVT-1401-treated patients (N=10, pooled analysis) showed a mean 3.8-point improvement on the MG-ADL scale vs. a mean decline of +0.6 for placebo (p=0.029).
    • MG-ADL responder rates (>2 point improvement) were 60% for IMVT-1401-treated patients vs. 20% for placebo.
    • MG-ADL deep responder rates (>6 point improvement) were 40% for IMVT-1401-treated patients vs. 0% for placebo.
  • IMVT-1401-treated patients also showed a highly significant improvement on the MGC scale (composite of patient and physician assessments), with an average improvement of 8.0 points vs. a mean decline of +1.4 for placebo (p = 0.006).
    • MGC deep responder rates (>10 point improvement) were 40% for IMVT-1401-treated patients vs. 0% for placebo.
  • Strong IgG reduction: 59% for 340mg dose and 76% for 680mg dose.
  • Good safety profile, with no SAE or AE and no imbalance in headaches. Reduction in albumin were consistent with prior studies.

Immunovant will proceed with a Phase 3 trial in H1 2021.

Three new indications are expected to be announced over the next 12 months.

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August 20, 2020

Impact: Moderate

  • Gilead and Tango will expand a 2018 agreement into a multi-year discovery, development, and commercialization collaboration of novel immune evasion therapies in oncology.
  • The deal structure includes:
    • $125M up-front payments and a $20M equity investment.
    • Opt-in rights to up to 15 targets up to $410M per program in total payments from Gilead to Tango.
    • Gilead will have worldwide rights for programs over the next seven years, with the option to pay extension fees for Tango to lead activities through early clinical development.
    • In return, Tango will receive low double-digit royalties on net sales, milestone payments and royalties on ex-U.S. sales, and have the option to co-develop and co-promote lead products for up to five programs in the U.S.
  • The agreement will give Gilead access to Tango’s CRISPR-based functional genomics target discovery platform to explore investigational immune evasion targets in oncology.

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August 6, 2020

Impact: High

Biogen and Denali Therapeutics announced an agreement to co-develop and co-commercialize Denali’s small molecule LRRK2 franchise for PD. Biogen receives the rights to opt into two programs, and rights of first negotiation for two other programs – both related to Denali’s blood-brain barrier technology, Transport Vehicle. Under terms of the agreement, Biogen will make an upfront payment of $560M, with a $465M equity investment in Denali (through stock purchase of 11.2% outstanding stock). Denali is eligible to receive up to $1.125B in potential milestones. Read more

July 22, 2020

Impact: High

  • GENFIT has officially terminated its pivotal RESOLVE-IT trial of elafibranor for the treatment of NASH with fibrosis after it failed an interim analysis back in May.
  • The trial did not meet the predefined primary surrogate efficacy endpoint of NASH resolution without worsening of fibrosis in the ITT population of 1,070 patients.
  • Following a detailed review of the full interim efficacy dataset, GENFIT determined that the investment needed to continue the trial was not justified, as it was unlikely to support a regulatory filing.
  • The company plans to share key learnings, including upcoming results from the second reading of liver biopsies that will help better understand inter-reader variability and its impact.
  • GENFIT will continue to develop elafibranor in primary biliary cholangitis (PBC) and is committed to initiate a phase 3 program following positive phase 2 data in this indication. The company will announce its updated corporate strategy in September 2020.

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July 17, 2020

Impact: Moderate

  • ADC Therapeutics has dosed the first patient in the pivotal phase 2 portion of its phase 1/2 LOTIS 3 trial (NCT03684694) of loncastuximab tesirine plus ibrutinib in R/R DLBCL or MCL (Mantle Cell Lymphoma).
  • The phase 2 portion is to enroll three cohorts: non-germinal center B cell (GCB)-like DLBCL, GCB DLBCL, and MCL.
  • Interim data for the phase 1 portion was presented at EHA 2020, as follows:
    • Overall response rate (ORR): 75% (complete response [CR] rate: 58.3%)
    • Grade ≥3 treatment-emergent adverse events (TRAE): thrombocytopenia (20%), anemia (12%).
    • Recommended phase 2 dose: 60 µg/kg.

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July 8, 2020

Impact: High

  • FDA has issued a CRL (Complete Response Letter) in response to the sBLA for the combination of Keytruda/Lenvima (pembrolizumab/lenvatinib) to treat first-line (1L) unresectable HCC (hepatocellular carcinoma). This application was supported by Merck and Eisai.
  • The application was based on data from the phase 1b single-arm KEYNOTE-524 (Study 116; NCT03006926) trial. The combination had previously received Breakthrough Therapy Designation and the companies sought Accelerated Approval. Key efficacy data from -524 were presented at ASCO 2020 and included:
    • mOS: 22 months
    • ORR (Objective Response Rate): 36% (CR rate: 1%)
    • mDoR (median Duration of Response): 12.6 months
  • According to the press release, the main reason for the CRL was that Keytruda/Lenvima did not represent a meaningful advantage over currently available therapies in 1L HCC. Notably, the combination of Tecentriq/Avastin (atezolizumab/bevacizumab) in 1L HCC was approved 4 weeks earlier on the basis of benefits observed for mOS (median Overall Survival) and mPFS (median Progression-Free Survival) in a phase 3 active comparator study.
  • Merck/Eisai still plan to submit for a full approval of Keytruda/Lenvima based on the LEAP-002 trial in 1L HCC. This trial is fully enrolled.

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July 2, 2020

Impact: High

Regeneron and Sanofi have announced that a Regeneron-led phase 3 U.S. trial of Kevzara (sarilumab) in patients with COVID-19 failed to meet its primary or key secondary endpoints and has been stopped early. 

The adaptive-design trial was enrolling patients with severe or critical COVID-19. The primary endpoint was a ≥1-point improvement on a 7-point ordinal scale in critical patients who were receiving mechanical ventilation at baseline; 194 patients were evaluable for the primary analysis. Patients had received Kevzara 400mg or placebo in addition to standard of care (SOC). 

The interim results showed minor positive trends with Kevzara in the primary analysis group, but statistical significance was not achieved and the positive trends were outweighed by negative trends in a subgroup of critical patients who were not receiving mechanical ventilation at baseline.

Based on these outcomes, the trial has been stopped, including a partially enrolled, higher dose cohort (800mg). Detailed results will be submitted to a peer-reviewed journal for publication later in the year. 

A separate Sanofi-led trial outside of the U.S. evaluating a different Kevzara regimen in patients with severe or critical disease is ongoing. The same Independent Data Monitoring Committee is overseeing both trials and has recommended continuation of the ex-U.S. trial. Results are expected in Q3 2020. Read more

June 23, 2020

Impact: Moderate

  • Researchers at the University of Oxford reported results from a randomized study of patients with severe cases of COVID-19, with either oral or intravenous administration of the widely available steroid dexamethasone, compared to usual care.
  • 2,104 patients were randomized to receive dexamethasone 6 mg once per day (either by mouth or by intravenous injection) for ten days and were compared with 4,321 patients randomized to usual care alone.
  • Dexamethasone reduced deaths by one-third in ventilated patients and by one fifth in other patients receiving oxygen only. There was no benefit among those patients who did not require respiratory support.
  • Full results have not yet been published or peer reviewed.
  • The RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial was established as a randomized clinical trial to test a range of potential treatments for COVID-19, including low-dose dexamethasone. Over 11,500 patients have been enrolled at over 175 NHS hospitals in the UK.

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June 23, 2020

Impact: High

  • Inventiva has released topline results from the phase 2b NATIVE trial of its pan-PPAR agonist, lanifibranor, for the treatment of NASH.
  • The primary endpoint of the trial, the Steatosis Activity Fibrosis (SAF) score at Week 24 was met, along with all other secondary outcomes at the same time point, including NASH resolution with no worsening of fibrosis and improvement of liver fibrosis with no worsening of NASH.
  • The proportion of patients achieving a reduction in SAF score of ≥2 at Week 24 was 41% and 49% in the lanifibranor 800mg and 1200mg treatment groups respectively, compared with 27% in the placebo group (p=0.061 and p=0.004).

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