On July 9, 2019 REVOLUTION Medicines, Inc., a clinical-stage leader in the discovery and development of novel small molecule inhibitors of frontier oncology targets within notorious pathways, reported the closing of a $100 million Series C equity financing (Press release, Revolution Medicines, JUL 9, 2019, View Source [SID1234553325]). Proceeds will support continued advancement of the company’s pipeline, which includes programs addressing elusive targets within the RAS pathway such as KRASG12C(GTP) and other specific tumorigenic mutants of RAS. The financing was supported by a syndicate of premier life science investors led by Boxer Capital of the Tavistock Group and joined by Cormorant Capital, Deerfield Management, Fidelity Management & Research Company, Vivo Capital and Biotechnology Value Fund, as well as all Series B investors, including Nextech Invest, Schroder Adveq, The Column Group, Third Rock Ventures and Casdin Capital.

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"This strong support comes at an exciting time for REVOLUTION Medicines as we advance novel programs addressing multiple frontier oncology targets within the resilient and adaptable RAS cancer pathway, including our clinical-stage inhibitor of SHP2," said Mark A. Goldsmith, M.D., Ph.D., president and chief executive officer of REVOLUTION Medicines. "Our position at the forefront of RAS pathway-focused therapeutics development is powered by a deep commitment to RAS pathway biology and our differentiated drug discovery capabilities. Our innovation engine enables the creation of sophisticated drug candidates that inhibit protein targets that defy conventional drug discovery methods, which we believe will bring the promise of targeted therapy to inadequately served cancer patients."

SHP2 Program

The company’s lead clinical development candidate, RMC-4630, is a potent, orally bioavailable small molecule that selectively inhibits the activity of SHP2, a protein that plays a central role in modulating cell growth signaling activity through the RAS pathway. RMC-4630, which is the focus of an exclusive global research, development and commercialization agreement with Sanofi, is currently being evaluated in a Phase 1/2 clinical program for a range of tumor types featuring specific oncogenic mutations.

Targeted Mutant RAS Program

REVOLUTION Medicines is advancing multiple innovative programs directed toward inhibiting the oncogenic actions of a broad range of mutants within the RAS protein family and across multiple RAS isoforms. The most advanced of these programs is focused on KRASG12C(GTP), which has been shown to drive multiple cancer types including lung, colorectal, endometrial and pancreatic cancers, among others. This target has been the focus of significant recent attention following the presentation of promising early-stage data regarding a first-generation KRASG12C inhibitor, AMG 510, at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting.

First-generation inhibitors, including those profiled at ASCO (Free ASCO Whitepaper) 2019, target the inactive (GDP-bound) state of mutant KRAS. By contrast, REVOLUTION Medicines has leveraged its proprietary tri-complex drug discovery platform to create novel second-generation compounds designed to selectively bind to and inhibit the active, oncogenic (GTP-bound) forms of various RAS mutants. Preclinical evidence suggests that this mechanism of action confers a superior biological profile compared with first-generation inhibitors and thereby potentially offers significant competitive advantages. The company’s KRASG12C(GTP) program is currently advancing through lead optimization.

For the financing, REVOLUTION Medicines received legal counsel from Latham and Watkins, LLP and strategic advice from Guggenheim Securities.

Other News

In related company news, REVOLUTION Medicines has completed its integration of the oncology-focused assets from Warp Drive Bio into its in-house technology platform and product pipeline following its acquisition of the company in late 2018. The company has also completed the recently announced divestiture of Warp Drive Bio’s antibiotic-related genome mining platform in order to maintain focus on its oncology mission.

On July 9, 2019 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "Company"), a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune diseases, reported an equity financing to raise approximately A$10 million comprising the following (Press release, Immutep, JUL 9, 2019, View Source [SID1234538762]):

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a placement of 190.5 million new fully paid ordinary shares in the Company ("Shares") to multiple new and existing Australian and foreign institutional and professional investors at an issue price of A$0.021 per Share ("Offer Price") (representing a 16.7% discount to the volume weighted average price ("VWAP") of the Company’s Shares as traded on the ASX over the 5 days up to and including 4 July 2019) ("Placement"), raising a total of A$4 million before transaction-related expenses.

a 1 for 11.8 fully underwritten pro rata non-renounceable entitlement offer of new Shares at the Offer Price to raise approximately A$6 million ("Entitlement Offer").

The New Shares to be issued under the Placement will be issued under the Company’s available placement capacity under ASX Listing Rule 7.1 and 7.1A.

Use of Funds

The Company will use the proceeds received from the Placement and the Entitlement Offer to finance its LAG-3 related clinical program in immuno-oncology and autoimmune disease. This includes the ongoing clinical development of eftilagimod alpha ("efti" or "IMP321"), via its TACTI-mel, TACTI-002, and INSIGHT clinical studies, development of IMP761 and for general corporate purposes.

Subject to sufficient and clinically meaningful data from the Company’s most advanced and potentially pivotal clinical trial, AIPAC (expected in Q1 of calendar year 2020) the funds raised may also be applied to pursue the appropriate regulatory pathways for efti and to explore ways to bridge Immutep’s research efforts in metastatic breast cancer to the US.

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Immutep CEO Marc Voigt commented: "We are pleased to welcome new institutional investors to our register and receive further support from our existing institutional shareholders in Australia and overseas. We are also providing eligible existing shareholders with the opportunity to participate on the same terms via the Entitlement Offer. We are pleased with the excess demand and support that Immutep is receiving ahead of reporting first data from our Phase IIb AIPAC trial in Q1 of calendar year 2020.

"Immutep has built a strong clinical trial pipeline and has a data-heavy period ahead. This financing provides important funding for our immuno-oncology and autoimmune programs. In particular, we will allocate funding for our value creating work for efti."

Details of Entitlement Offer

Under the Entitlement Offer, eligible shareholders are invited to subscribe for 1 new Share for every 11.8 existing Shares (Entitlement) held as at 7.00pm (Sydney, Australia time) on 12 July 2019 (Record Date) at an offer price of A$0.021 per new Share.

Eligible shareholders may also apply for New Shares in excess of their Entitlement (Additional New Shares) at the Offer Price, up to a maximum of A$20,000. The Company may apply any scale-back to applications for Additional New Shares in its absolute discretion.

The Offer Price of A$0.021 represents:

a discount of 16.0% to the closing price of the Shares on 4 July 2019;

a 16.7% discount to the VWAP of the Company’s Shares as traded on the ASX over the 5 days up to and including 4 July 2019; and

a 14.3% discount to the theoretical ex-rights price.1

Approximately 287.2 million new Shares will be issued under the Entitlement Offer. Shares issued under the Entitlement Offer will rank equally with existing Shares as at their date of issue.

The Entitlement Offer has been fully underwritten by Bell Potter Securities Limited.

Eligibility to participate in Entitlement Offer

Shareholders with a registered address in Australia or New Zealand on the Record Date (Eligible Shareholders) will be invited to participate in the Entitlement Offer. The Entitlement Offer will open on 16 July 2019.

Entitlements are non-renounceable and cannot be traded on the ASX or any other exchange, nor can they be privately transferred. Shareholders who do not take up their Entitlements in full will not receive any payment or value for those Entitlements they do not take up.

The theoretical ex-rights price (TERP) is a theoretical price at which Shares should trade immediately after the ex-date of the Entitlement Offer. The TERP is a theoretical calculation only and the actual price at which Shares trade immediately after the ex-date for the Entitlement Offer will depend on many factors and may not be equal to TERP.

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Further details on the Entitlement Offer are set out in the Entitlement Offer booklet provided to ASX today. These documents contain important information including key risks and foreign selling restrictions with respect to the Entitlement Offer.

Details of the Placement

The Company has secured commitments from institutional investors to subscribe for A$4 million in new Shares. Shares to be issued under the Placement will be issued at the Offer Price and will be issued on 18 July 2019.

Indicative Timetable

Event

Date

Placement and Entitlement Offer announced Pre-market open 9 July 2019
Lodge Appendix 3B, cleansing notice and ‘Appendix 3B’ letter for Entitlement Offer Pre-market open 9 July 2019
Shares quoted on an ‘ex’ basis 11 July 2019
Record date for the Entitlement Offer (Record Date) 12 July 2019
Entitlement Offer opens 16 July 2019
Settlement of Placement 16 July 2019
Issue of Shares under Placement 17 July 2019
Normal settlement trading of Shares issued under Placement 18 July 2019
Entitlement Offer closes 30 July 2019
New Shares and Additional New Shares quoted on a deferred settlement basis 31 July 2019
Issue of New Shares and Additional New Shares 6 August 2019
Normal trading of New Shares and Additional New Shares expected to commence on ASX 7 August 2019
Dates and times are indicative only and subject to change. All times and dates refer to Sydney, Australia time.

The Company reserves the right, subject to the Corporations Act, ASX Listing Rules and other applicable laws, to vary the dates of the Placement and Entitlement Offer without prior notice, including extending the Placement and Entitlement Offer or accepting late applications, either generally or in particular cases, or to withdraw the Entitlement Offer without prior notice. Applicants are encouraged to submit their personalised Entitlement and Acceptance Forms as soon as possible. No cooling-off rights apply to applications submitted under the Entitlement Offer. The commencement of quotation of new Shares is subject to confirmation from ASX.

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Bell Potter Securities Limited acted as the Lead Manager to the Placement and Entitlement Offer.

About Immutep

Immutep is a globally active biotechnology company that is a leader in the development of immunotherapeutic products for the treatment of cancer and autoimmune disease. Immutep is dedicated to leveraging its technology and expertise to bring innovative treatment options to market for patients and to maximize value to shareholders. Immutep is listed on the Australian Securities Exchange (IMM), and on the NASDAQ (IMMP) in the United States.

Immutep’s current lead product candidate is eftilagimod alpha ("efti" or "IMP321"), a soluble LAG-3Ig fusion protein based on the LAG-3 immune control mechanism. This mechanism plays a vital role in the regulation of the T cell immune response. Efti is currently in a Phase IIb clinical trial as a chemoimmunotherapy for metastatic breast cancer termed AIPAC; a Phase II clinical trial being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada) referred to as TACTI-002 (Two ACTive Immunotherapies) to evaluate a combination of efti with KEYTRUDA (pembrolizumab) in several different solid tumours (clinicaltrials.gov identifier NCT03625323); a Phase I clinical trial being conducted in collaboration with Merck KGaA, Darmstadt, Germany and Pfizer Inc. referred to as INSIGHT-004 to evaluate a combination of efti with avelumab (clinical trials.gov identifier NCT03252938); and a Phase I combination therapy trial in metastatic melanoma termed TACTI-mel (clinicaltrials.gov identifier NCT02676869).

Further information can be found on the Company’s website www.immutep.com or by contacting:

U.S. Investors:

Jay Campbell, Chief Business Officer, Immutep Limited

On July 9, 2019 ImaginAb Inc., a clinical stage immuno-oncology imaging company, reported that it has entered into a non-exclusive license and collaboration agreement with Roche (SIX: RO, ROG; OTCQX: RHHBY) (Press release, ImaginAb, JUL 9, 2019, View Source [SID1234537478]). Under the terms of the agreement, Roche will use ImaginAb’s novel minibody CD8 T cell imaging agent in immuno-oncology clinical trials for multiple types of cancers. Financial terms of the agreement were not disclosed.

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ImaginAb’s CD8 T cell imaging agent is designed to be used with PET scan technology to non-invasively determine changes in CD8 T cell tumor infiltrates induced by immunotherapy treatments. This investigational approach has the potential to guide the development of immunomodulatory agents and combinations by assessing whether a patient’s immune system responds to such agents, thereby offering an early prediction of therapeutic response.

Ian Wilson, Chief Executive Officer of ImaginAb, said: "We are thrilled about our collaboration with Roche, a leading pharmaceutical company focused on cancer treatment and diagnostics. We believe our platform offers real potential to accelerate clinical development of next-generation immunotherapeutics and ultimately provides guidance for personalized use of mono or combination therapies for patients suffering from different types of cancer. This collaboration further expands the network of companies, clinical investigators, and PET centers utilizing our 89-Zr CD8 ImmunoPET technology, demonstrating the utility and value of this technology in the field of immuno-oncology."

For further information please contact:

ImaginAb

Ian Wilson
Email: [email protected]
Phone: +1 310 645 1211

Optimum Strategic Communications

Mary Clark, Supriya Mathur, Manel Mateus
Email: [email protected]
Phone: +44 20 3950 9144

On July 9, 2019 NANOBIOTIX (Euronext: NANO – ISIN: FR0011341205), a clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, reported that the previously reported results from the Phase II/III Act.In.Sarc trial evaluating NBTXR3 in patients with advanced STS have been published online in The Lancet Oncology (Press release, Nanobiotix, JUL 9, 2019, View Source [SID1234537453]).

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The registration study met its primary (pCR) and secondary (R0 rate) endpoints. The increased proportion of patients with pCR among those given NBTXR3 as a single injection prior to standard of care RT when compared to RT alone (approximately twice as many), provides robust justification for the efficacy of nanoparticle-enhanced tumor cell death. The overall safety profile of NBTXR3 activated by RT was similar to RT alone, with manageable and reversible transient immune reactions observed in those treated with NBTXR3 and RT. More detail on the results can be found here.

The data from the Act.In Sarc trial were the basis for first European market approval (CE marking) of NBTXR3 in advanced STS of the extremity and chest wall, under the brand name Hensify. With STS results validating the efficacy and safety profile of the product, the company will continue its development strategy to evaluate NBTXR3 in multiple global (US, EU and APAC) clinical trials with a focus including but not limited to: head and neck, liver, lung and prostate cancer, as well as tumors that may benefit from NBTXR3 in combination with immune-oncology agents.

About Phase II/III Act.In.Sarc Study

Nanobiotix and its partner, PharmaEngine treated 179 patients in 32 sites across 11 countries in Europe and Asia. The Global Principal Investigator is Pr. Sylvie Bonvalot, MD, PhD (Institut Curie, Paris, France).

Primary Endpoint
Pathological Complete Response Rate (pCR): A pathological complete response is defined as the presence of less than 5% of residual malignant viable cells in the surgically removed tissue. The primary endpoint compared the proportion of patients with pCR between the two randomized arms. This was determined by an independent pathological central review according to Wardelmann et al., 2016.

Key Secondary Endpoint
Resection Margin Status: The resection margin status is evaluating the quality of surgery. Surgery remains the mainstay of care for advanced soft tissue sarcoma. The primary surgical objective is the complete removal of the tumor with negative resection margins (R0). Several retrospective studies suggest that surgical margin status predicts the risk of local and distant recurrence. In particular, negative surgical margins are significantly correlated to increased patients’ survival.

About NBTXR3
NBTXR3 is a first-in-class product designed to destroy tumors through physical cell death when activated by radiotherapy.

NBTXR3 has a high degree of biocompatibility, requires one single administration before the first radiotherapy treatment
session, and has the ability to fit into current worldwide standards of radiation care. The physical mode of action of NBTXR3
makes it applicable across solid tumors such as lung, prostate, liver, glioblastoma, and breast cancers.

NBTXR3 is actively being evaluated in head and neck cancer with locally advanced squamous cell carcinoma of the oral cavity or
oropharynx in elderly and frail patients unable to receive chemotherapy or cetuximab with very limited therapeutic options.
Promising results have been observed in the phase I/II trial regarding the local control of the tumors. In the United States,
based on the discussions with the Food and Drug Administration that occurred in the first half of 2019, the Company plans to
begin the clinical trial authorization process in the second half of 2019 and commence a phase II/III clinical trial in locally
advanced head and neck cancers.

Nanobiotix is also running an Immuno-Oncology development program. In the United States, the Company received approval
from the Food and Drug Administration to launch a clinical trial of NBTXR3 activated by radiotherapy in combination with antiPD-1 antibodies in lung, and head and neck cancer patients (head and neck squamous cell carcinoma and non-small cell lung
cancer).

The other ongoing NBTXR3 trials are treating patients with liver cancers (hepatocellular carcinoma and liver metastasis), locally
advanced or unresectable rectal cancer in combination with chemotherapy, head and neck cancer in combination with
concurrent chemotherapy, and prostate adenocarcinoma.
Further, the company has a large-scale, comprehensive clinical research collaboration with The University of Texas MD
Anderson Cancer Center (9 new phase I/II clinical trials in the United States) to evaluate NBTXR3 across head and neck,
pancreatic, thoracic, lung, gastrointestinal and genitourinary cancers.

On July 9, 2019 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for CLR 131 in relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL) (Press release, Cellectar Biosciences, JUL 9, 2019, View Source [SID1234537452]). CLR 131 is the company’s small-molecule, cancer-targeting radiotherapeutic Phospholipid Drug Conjugate (PDC) designed to deliver cytotoxic radiation directly and selectively to cancer cells and cancer stem cells. It is currently being evaluated in Cellectar’s ongoing Phase 2 CLOVER-1 clinical study in patients with relapsed or refractory select B-Cell lymphomas.

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"We are pleased to receive FDA’s Fast Track Designation for CLR 131. This designation supports our efforts to more rapidly provide a new therapeutic option for patients with relapsed or refractory DLBCL, a disease that typically has a very poor prognosis and low rates of survival," said James Caruso, president and CEO of Cellectar. "As announced last year, data from the DLBCL cohort in our ongoing CLOVER-1 trial showed an encouraging 33% overall response rate at the time of the interim assessment. Patients prior to the interim assessment received a single 25.0 mCi/m2 dose of CLR 131. Dosing in the Phase 2 CLOVER-1 study has increased, and patients are now receiving 37.50 mCi/m2 fractionated in two administrations of CLR 131. We are optimistic that CLR 131 has the potential to provide a meaningful treatment option for these patients and look forward to additional data in 2019."

Fast Track Designation

Fast Track Designation is granted to drugs being developed for the treatment of serious or life-threatening diseases or conditions where there is an unmet medical need. The purpose of the Fast Track Designation provision is to help facilitate development and expedite the review and potential approval of drugs to treat serious and life-threatening conditions.

Sponsors of drugs that receive Fast Track Designation have the opportunity for more frequent interactions with the FDA review team throughout the development program. These can include meetings to discuss study design, data required to support approval, or other aspects of the clinical program. Additionally, products that have been granted Fast Track Designation may be eligible for priority review of a New Drug Application (NDA) and the FDA may consider reviewing portions of an NDA before the sponsor submits the complete application (Rolling Review).

About the Phase 2 CLOVER-1 Trial

CLOVER-1 is a Phase 2 study of CLR 131 being conducted in approximately 10 leading cancer centers in the United States in patients with relapsed or refractory B-Cell hematologic cancers. The hematologic cancers being studied in the trial include multiple myeloma (MM), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and diffuse large B-Cell lymphoma (DLBCL).

The study will enroll up to 80 patients. Its primary endpoint is clinical benefit response (CBR), with additional endpoints of overall response rate (ORR), progression free survival (PFS), median overall survival (OS) and other markers of efficacy following a fractionated dose of 37.5mCi/m2 of CLR 131 administered in two 30-minute infusions of 18.75mCi/m2 of CLR 131 administered on day 1 and day 8, with the option for a second dose cycle approximately 75-180 days later. The company expects to report topline data in 2019.

Cellectar was awarded approximately $2 million in non-dilutive grant funding from the National Cancer Institute to help fund the trial. More information about the trial, including eligibility requirements, can be found at www.clinicaltrials.gov, reference NCT02952508.

About CLR 131

CLR 131 is a small-molecule, targeted Phospholipid Drug Conjugate (PDC) designed to deliver cytotoxic radiation directly to cancer cells, while limiting exposure to healthy cells. CLR 131 is the company’s lead product candidate and is currently being evaluated in a Phase 2 study in B-Cell lymphomas, and two Phase 1 dose-escalating clinical studies, one in multiple myeloma and one in pediatric solid tumors and lymphoma. CLR 131 was granted Orphan Drug designation for the treatment of multiple myeloma, and was granted Orphan Drug and Rare Pediatric Disease for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma.