On December 10, 2019 SCYNEXIS, Inc. (NASDAQ: SCYX) reported the pricing of its previously announced underwritten public offering of 38,888,889 shares of common stock and warrants to purchase up to 38,888,889 shares of common stock (Press release, Scynexis, DEC 10, 2019, View Source [SID1234552197]). Each share of common stock and warrant to purchase one share of common stock are being sold at a combined public offering price of $0.90 per share and accompanying warrant. The gross proceeds to SCYNEXIS from this offering are expected to be approximately $35 million, before deducting underwriting discounts and commissions and other estimated offering expenses, and excluding the exercise of any warrants. All of the shares of common stock and warrants are being offered by SCYNEXIS.

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H.C. Wainwright & Co. is acting as sole book-running manager for the offering.

The warrants will have an exercise price of $1.10 per share and exercise period commencing immediately upon issuance and an expiration date of the earlier of (i) such date that is six months after SCYNEXIS publicly announces the approval from the U.S. Food and Drug Administration for ibrexafungerp for the treatment of vulvovaginal candidiasis and (ii) June 12, 2023. There is no established public trading market for the warrants, and SCYNEXIS does not expect a market to develop.

In addition, SCYNEXIS has granted the underwriters a 30-day option to purchase up to an additional 5,833,333 shares of common stock and/or warrants to purchase up to 5,833,333 shares of common stock, at the public offering price, less the underwriting discounts and commissions. The offering is expected to close on or about December 12, 2019, subject to customary closing conditions. A shelf registration statement relating to the securities being sold in this offering was filed with the U.S. Securities and Exchange Commission (SEC) on August 31, 2018, and was declared effective on September 14, 2018. The offering is being made only by means of a prospectus supplement and accompanying prospectus. A preliminary prospectus supplement and accompanying prospectus relating to the offering were filed with the SEC and a final prospectus supplement and accompanying prospectus will be filed with the SEC and will be available for free on the SEC’s website located at View Source When available, electronic copies of the final prospectus supplement and accompanying prospectus relating to the public offering may be obtained by contacting H.C. Wainwright & Co., LLC, 430 Park Avenue, 3rd Floor, New York, NY 10022, or by telephone at (646) 975-6996, or by email to [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On December 10, 2019 Celyad (Euronext Brussels and Paris, and Nasdaq: CYAD), a clinical-stage biopharmaceutical company focused on the development of CAR-T cell therapies, reported updates to the company’s autologous NKG2D-based CAR-T development program for the treatment of relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) at the American Society of Hematology (ASH) (Free ASH Whitepaper) 61st Annual Meeting, which is being held from December 7-10, 2019 in Orlando, Florida (Press release, Celyad, DEC 10, 2019, View Source [SID1234552196]).

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Filippo Petti, CEO of Celyad, commented, "Over the past few months we have worked diligently to transition our proprietary OptimAb manufacturing process to become the cornerstone of our autologous CAR-T program for the treatment of relapsed/refractory acute myeloid leukemia and myelodysplastic syndromes. We are encouraged by the body of data generated to date by our lead autologous candidate CYAD-01 for the treatment of AML and MDS, especially given its tolerability profile and anti-leukemic activity."

"We are excited to further evaluate our NKG2D-based CAR-T approach using our OptimAb manufacturing process, which generates a higher frequency of less differentiated CAR-T cells that exhibit enhanced anti-tumor activity in preclinical studies. Overall, we believe the process gives us the best opportunity for success across both autologous product candidates, CYAD-01 and CYAD-02. Along with our ongoing DEPLETHINK trial, the key next steps for our broad r/r AML and MDS program include the expansion of the THINK trial and initiation of the CYCLE-1 trial as we look to establish NKG2D as an important target for the treatment of difficult-to-treat malignancies", continued Mr. Petti.

CYAD-01 THINK Phase 1 Trial

Sixteen patients have been enrolled to date in the trial evaluating CYAD-01 administered as a multiple injection with a biweekly schedule and an additional nine patients have been enrolled in the dose dense (weekly) schedule in the dose escalation segment of the trial
CYAD-01 without preconditioning chemotherapy was generally reported to be well-tolerated, with 11 out of 25 patients experiencing grade 3/4 treatment-related adverse events (AEs). Cytokine release syndrome (CRS) occurred in 13 patients, with four grade 3 and two grade 4 events, which showed rapid resolution following the appropriate treatment, including tocilizumab. Two dose-limiting toxicities were reported at dose level 3 (3 billion cells per infusion), including one CRS grade 4 (biweekly) and one CRS grade 3 (dose dense schedule). No treatment-related neurotoxicity AEs were reported
Overall, eight patients out of 15 evaluable patients treated with CYAD-01 produced with the prior manufacturing process demonstrated anti-leukemic activity. Five out of the eight patients exhibited an objective response. In addition, one patient is exhibiting disease stabilization of over three months
Patients treated within the CYAD-01 dose-dense (weekly) schedule cohorts of the trial did not demonstrate an improvement in clinical outcome as compared to patients treated with the biweekly dosing schedule. However, patients enrolled in the dose-dense schedule cohorts appeared to have greater bone marrow blasts infiltration and to be more pancytopenic at baseline compared to patients enrolled in the biweekly dose escalation segment of the trial
Most of the anti-leukemic activity observed in the trial, except for the two patients who bridged to an allogeneic human stem cell transplant, experienced a short durability of response
To date, anti-leukemic activity appears predominantly observed in patients initially diagnosed with non-adverse (ELN 2017, AML) or non-very high (IPSS-R, MDS) risk stratification categories. Additional patients are needed in the trial to better assess the observation
Company plans to progress to the expansion segment of the THINK trial to further evaluate CYAD-01 produced with the OptimAb manufacturing process. Enrollment in the expansion segment of the trial is expected to begin in first quarter 2020 with preliminary data anticipated by the end of first half 2020
CYAD-01 DEPLETHINK Phase 1 Trial

Nine patients have been enrolled in the trial evaluating CYAD-01 produced with the prior mAb manufacturing process following preconditioning chemotherapy cyclophosphamide and fludarabine, or CyFlu, at the first two dose levels of the dose escalation segment of the trial
CYAD-01 produced with the mAb manufacturing process was generally reported to be well-tolerated following preconditioning chemotherapy. At the first CYAD-01 infusion of the consolidation cycle (3 billion cells per infusion), one patient experienced both grade 4 cytokine release syndrome (CRS) and grade 3 CAR-T cell-related encephalopathy and another patient experienced grade 3 CRS. Both patients recovered following the appropriate treatment, including tocilizumab
Preconditioning chemotherapy led to improved, dose-dependent engraftment of CYAD-01 cells as compared to cells infused with no preconditioning
To date, no objective response has been observed at the first two dose levels of the trial in patients treated with CYAD-01 produced with the mAb manufacturing process
In September 2019, the company announced the successful administration of CYAD-01 produced with the OptimAb manufacturing process to a patient enrolled in cohort 3 (300 million cells per infusion) of the trial
Enrollment in the trial is ongoing with plans to dose escalate up to one billion cells per infusion in cohort 4. Preliminary data evaluating CYAD-01 produced with the OptimAb manufacturing process from cohorts 3 and 4 are expected by the end of first half 2020
CYAD-02 CYCLE-1 Phase 1 Trial

In November 2019, the company initiated the dose-escalation Phase 1 CYCLE-1 trial (NCT04167696), which will evaluate the safety and clinical activity of the next-generation, autologous NKG2D-based CAR-T candidate CYAD-02, produced with the OptimAb manufacturing process following preconditioning chemotherapy CyFlu in patients with r/r AML and MDS
CYAD-02 incorporates shRNA SMARTvector technology licensed from Horizon Discovery to target the NKG2D ligands MICA and MICB. shRNA-mediated knockdown of MICA and MICB expression on NKG2D CAR-T cells has been shown to enhance in vitro expansion of the CAR-T cells and enhanced engraftment and persistence in preclinical models as compared to CYAD-01 produced with the mAb process
Enrollment in the CYCLE-1 trial is expected to begin in early 2020 with preliminary data anticipated during second half 2020
About THINK Phase 1 Trial

The THINK trial (NCT03018405) is an open-label, dose-escalation Phase 1 trial assessing the safety and clinical activity of multiple CYAD-01 administrations without prior preconditioning. The dose escalation segment of the trial evaluated three dose levels (300 million, 1 billion and 3 billion cells per infusion) of one cycle of three CYAD-01 administrations with two-week intervals. In 2018, the THINK trial was amended to add two cohorts to assess a more frequent dosing schedule of CYAD-01 for the treatment of r/r AML. The cohorts will evaluate six injections of CYAD-01 without preconditioning over two months of administration. The first cycle includes three infusions of CYAD-01 separated by one-week intervals. The second cycle includes three infusions of CYAD-01 separated by two-week intervals. Patients will either receive 1 billion cells per infusion (Cohort 10) or 3 billion cells per infusion (Cohort 11). The primary endpoint of the trial is safety and secondary endpoints include clinical activity and pharmacokinetics.

About DEPLETHINK Phase 1 Trial

In October 2018, Celyad initiated the DEPLETHINK Phase 1 trial (NCT03466320). The open-label, dose-escalation trial is designed to evaluate a single infusion of CYAD-01 following treatment with the standard preconditioning regimen of cyclophosphamide (300 mg/m²) and fludarabine (30 mg/m²), or CyFlu. The trial includes two different intervals between lymphodepletion and administration of CYAD-01. In addition, the trial is evaluating three dose levels of CYAD-01 including 100 million, 300 million and 1 billion cells per infusion, respectively. The primary endpoint of the trial is safety and secondary endpoints include clinical activity and pharmacokinetics.

About OptimAb Manufacturing Process

Celyad’s proprietary OptimAb manufacturing process utilizes a shortened cell culture and incorporates a selective PI3K inhibitor. This results in a product that is enriched for T cells with a memory-like phenotype. Preclinical data demonstrate that NKG2D-based CAR-T cell therapies produced using the OptimAb manufacturing process drive improved anti-tumor activity in an aggressive AML model compared to alternative manufacturing process.

On December 10, 2019 Stemline Therapeutics, Inc. (Nasdaq: STML), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics, reported data from ELZONRIS (tagraxofusp) Phase 1/2 clinical trials in myelofibrosis (oral presentation) and multiple myeloma, at the 2019 ASH (Free ASH Whitepaper) annual meeting (Press release, Stemline Therapeutics, DEC 10, 2019, View Source [SID1234552195]). The presentations are now available on the Stemline website, www.stemline.com, under the Scientific Presentations tab. Highlights of results are presented below.

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Myelofibrosis: Clinical Trial of ELZONRIS in Patients with Intermediate or High-Risk, Relapsed/Refractory Myelofibrosis (MF) – Oral presentation

ELZONRIS demonstrated efficacy (spleen size reductions and total symptom score [TSS] reductions) with a predictable and manageable safety profile, including in patients with poor prognostic factors, such as thrombocytopenia, CMML-type features/monocytosis, and clonal evolution
45% (9/20) of patients had symptom burden reduction, including 3 with symptom response per IWG-MRT 2013 MF response criteria
53% (8/15) of patients with baseline splenomegaly >= 5cm experienced a spleen size reduction; 20% (3/15) had a reduction >35% (specifically 100%, 47% and 46% reductions)
° 100% (5/5) of patients with CMML-type features/monocytosis experienced a spleen size reduction, and 40% (2/5) of these patients had a reduction >35%
° 64% (7/11) of patients with thrombocytopenia (platelet count < 100×109/L) experienced a spleen size reduction, and 18% (2/11) had a reduction >35%; 60% (3/5) of patients with thrombocytopenia (platelet count < 50×109/L) experienced a spleen size reduction, and 20% (1/5) had a reduction >35%

Most common treatment related adverse events (TRAEs) include alanine aminotransferase increase, headache, hypoalbuminemia (all 17%), anemia, and thrombocytopenia (both 14%)
° There was one case of capillary leak syndrome (CLS), which was grade 3
43% overall survival (OS) at 18 months; 29% OS at 2 years
Next Steps

Expansion of Phase 2 trial to include additional sites is underway
Patient enrollment and follow up continues to inform design of potential registration-directed trial of ELZONRIS in patients with relapsed/refractory MF, including poor prognosis patients with:
° Thrombocytopenia, and/or
° Monocytosis (CD123-overexpressed subsets)
Other areas of evaluation in MF

An additional ASH (Free ASH Whitepaper) presentation demonstrated that ELZONRIS, either alone or in combination with ruxolitinib, had preclinical activity against primary MF patient samples, including those in accelerated phase and with high molecular risk profiles where current therapeutic options beyond ruxolitinib are limited and CD123 expression is evident. These data support further evaluation of tagraxofusp in MF, not only as single agent but potentially in combination with Jak inhibitors.
Multiple Myeloma: Clinical Trial of ELZONRIS in Patients with Relapsed/Refractory Multiple Myeloma (MM)

ELZONRIS, in combination with pomalidomide (POM) and dexamethasone (DEX), demonstrated activity and a predictable and manageable safety profile in heavily pretreated patients with relapsed/refractory MM
56% of patients (5/9) who received ELZONRIS in combination with POM+DEX had partial responses (PRs)
° Notably, these patients also had decreases in their plasmacytoid dendritic cells (pDCs), a cell type implicated in myeloma growth and aggressiveness, and the cell of origin of blastic plasmacytoid dendritic cell neoplasm (BPDCN)
Given these clinical data, ELZONRIS may offer a novel mechanism of action and future therapeutic option for patients with MM
Next Steps

Given these encouraging early results, potential avenues for further ELZONRIS development are being assessed, including evaluating additional patients with this and/or potentially other regimens including in combination with daratumumab or novel agents such as XPO1 inhibitors. Moreover, the clinical knockdown of pDCs in MM patients may also be relevant with respect to other diseases, such as chronic myelomonocytic leukemia (CMML), MF and certain acute myeloid leukemia (AML) patient subsets, where pDCs have been similarly implicated in the aggressiveness of these malignancies.
About ELZONRIS
ELZONRIS (tagraxofusp), a CD123-directed cytotoxin, is approved by the U.S. Food and Drug Administration (FDA) and commercially available in the U.S. for the treatment of adult and pediatric patients, two years or older, with blastic plasmacytoid dendritic cell neoplasm (BPDCN). For full prescribing information in the U.S., visit www.ELZONRIS.com. In Europe, a marketing authorization application (MAA) is under review by the European Medicines Agency (EMA). ELZONRIS is also being evaluated in additional clinical trials in other indications including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), and acute myeloid leukemia (AML).

About BPDCN
BPDCN is an aggressive hematologic malignancy with historically poor outcomes and an area of unmet medical need. BPDCN typically presents in the bone marrow and/or skin and may also involve lymph nodes and viscera. The BPDCN cell of origin is the plasmacytoid dendritic cell (pDC) precursor. The diagnosis of BPDCN is based on the immunophenotypic diagnostic triad of CD123, CD4, and CD56, as well as other markers. For more information, please visit the BPDCN disease awareness website at www.bpdcninfo.com.

About CD123
CD123 is a cell surface target expressed on a wide range of myeloid tumors including blastic plasmacytoid dendritic cell neoplasm (BPDCN), certain myeloproliferative neoplasms (MPNs) including chronic myelomonocytic leukemia (CMML) and myelofibrosis (MF), acute myeloid leukemia (AML) (and potentially enriched in certain AML subsets), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). CD123 has also been reported on certain lymphoid malignancies including multiple myeloma (MM), acute lymphoid leukemia (ALL), hairy cell leukemia (HCL), Hodgkin’s lymphoma (HL), and certain Non-Hodgkin’s lymphomas (NHL). In addition, CD123 has been detected on some solid tumors as well as autoimmune disorders including cutaneous lupus and scleroderma.

On December 10, 2019 Spherix Incorporated (Nasdaq: SPEX) reported that it has closed the CBM BioPharma, Inc. transaction and is working to develop these cancer drugs (Press release, Spherix, DEC 10, 2019, View Source [SID1234552194]).

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Building on its successful investment in Hoth Therapeutics, Inc., Spherix now owns a diverse portfolio of early stage small-molecule anti-cancer therapeutics. The Spherix platform contains patented technology from leading universities and researchers and we seek to develop our innovative drugs through strong partnership with world renowned institutions, such as The University of Texas at Austin and Wake Forest University. The Company’s diverse pipeline of therapeutics includes therapies for pancreatic cancer, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Its pancreatic treatment has shown positive preclinical results for inhibiting pancreatic tumor growth in clinically relevant transgenic mouse models. The drug has also demonstrated the potential to overcome tumor cell resistance to current chemotherapeutic drugs. The Company’s AML drug is a next generation targeted therapeutic designed to overcome multiple resistance mechanisms observed with the current standard of care. In addition, Spherix is continually seeking to grow its pipeline to treat unmet medical needs in oncology.

Anthony Hayes, CEO of Spherix, stated, "The acquisition of these assets is yet another step in the transformation of Spherix into a diversified biotechnology company. These are exciting drugs and we intend to provide additional information about these drugs and the development plan moving forward. As the deal has evolved, we have successfully improved the terms for Spherix shareholders, we thank our shareholders for their support during this process."

On December 10, 2019 Onconova Therapeutics, Inc. (NASDAQ: ONTX) ("Onconova" or the "Company"), a Phase 3-stage biopharmaceutical company discovering and developing novel products to treat cancer, with an initial focus on myelodysplastic syndromes (MDS), reported the closing of its previously announced registered direct offering of 14,326,648 shares of its common stock and warrants to purchase up to 7,163,324 shares of its common stock, at a combined purchase price of $0.349 per share and associated warrant, for aggregate gross proceeds of approximately $5.0 million (Press release, Onconova, DEC 10, 2019, View Source [SID1234552192]). The registered direct offering priced at-the-market under Nasdaq rules.

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H.C. Wainwright & Co. acted as the exclusive placement agent for the offering.

The warrants issued in the offering have an exercise price of $0.287 per share and exercise period commencing immediately upon issuance and a term of five (5) years.

The Company intends to use the net proceeds from the offering for working capital and general corporate purposes, including advancing preparations for a planned New Drug Application (NDA) filing to the FDA for intravenous rigosertib in second-line higher-risk MDS in 2020. The Company surpassed 90% of the required enrollment of the INSPIRE Trial in November 2019 and anticipates reporting topline data in the first half of 2020, following full enrollment and reaching the number of required survival events. With the additional proceeds from the offering and the proceeds from the recent warrant exercise, the Company believes that it has the sufficient funds to extend operations and ongoing trials late into the third quarter of 2020.

The securities described above were offered and sold by the Company pursuant to a "shelf" registration statement on Form S-3 (Registration No. 333-221684), including a base prospectus, previously filed with and declared effective by the Securities and Exchange Commission (the "SEC") on December 28, 2017. The offering of the securities was made only by means of a prospectus supplement that forms a part of the registration statement. A final prospectus supplement and an accompanying base prospectus relating to the registered direct offering was filed with the SEC and is available on the SEC’s website located at View Source Electronic copies of the prospectus supplement and the accompanying base prospectus may also be obtained by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by phone at 646-975-6996 or e-mail at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.