On March 31, 2021 Sanofi reported that The U.S. Food and Drug Administration (FDA) has approved Sarclisa (isatuximab-irfc) in combination with carfilzomib and dexamethasone (Kd), for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received one to three prior lines of therapy (Press release, Sanofi, MAR 31, 2021, View Source [SID1234577459]).

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"In the Phase 3 IKEMA study, the addition of Sarclisa to carfilzomib and dexamethasone reduced risk of disease progression or death by 45%," said Thomas G. Martin, M.D., Associate Director, Myeloma Program, The University of California, San Francisco, Professor of Medicine, Adult Leukemia and Bone Marrow Transplantation Program and co-leader of the Hematopoietic Malignancies Program, Helen Diller Family Comprehensive Cancer Center. "This approval is an important advancement for patients whose disease has relapsed and reinforces the potential for Sarclisa to become a standard of care in relapsed or refractory multiple myeloma."

This marks the second FDA approval for Sarclisa, which is also approved in combination with pomalidomide and dexamethasone (pom-dex) for the treatment of adults with RRMM who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

"Treatment of patients with relapsed or refractory multiple myeloma remains challenging and the prognosis for patients experiencing multiple relapses unfortunately is poor," said Peter C. Adamson, M.D., Global Development Head, Oncology and Pediatric Innovation at Sanofi. "With this approval, Sarclisa is now included in two standard of care regimens for the treatment of patients with multiple myeloma as early as first relapse. Today’s milestone further supports our ambition for Sarclisa to become the anti-CD38 of choice for patients with relapsed or refractory multiple myeloma."

Sarclisa Phase 3 IKEMA pivotal trial results supporting approval

The FDA approval is based on data from the Phase 3 IKEMA study, a randomized, multi-center, open label clinical trial that enrolled 302 patients with relapsed multiple myeloma across 69 centers spanning 16 countries.1 In this study, Sarclisa added to Kd (Sarclisa combination therapy) reduced the risk of disease progression or death by 45% (hazard ratio 0.548, 95% CI 0.366-0.822, p=0.0032) versus standard of care Kd alone in patients with multiple myeloma. The median progression free survival (PFS) for Sarclisa combination therapy was not reached at the time of the pre-planned interim analysis. This study enrolled a difficult-to-treat patient population, including those who are elderly, have high cytogenetic risk or renal impairment. Overall, demographic and disease characteristics at baseline were balanced between the two treatment groups.2

Secondary endpoints of the IKEMA trial assessed the overall response rate (ORR) for Sarclisa combination therapy compared to Kd, including complete response (CR) and very good partial response (VGPR). There was no statistically significant difference in ORR, which remained similar for each arm at 86.6% for the Sarclisa combination therapy versus 82.9% for Kd (p=0.3859). The rate of CR was 39.7% in the Sarclisa combination therapy arm and 27.6% in the Kd arm. The rate of VGPR was 33% for patients receiving Sarclisa combination therapy and 28.5% for patients receiving Kd.2 At the time of the interim analysis, overall survival (OS) data were still immature.3

The most frequent adverse reactions (occurring in 20% or more of patients) for Sarclisa versus the control arm were upper respiratory tract infection (67% vs. 57%), infusion-related reactions (46% vs. 3.3%), fatigue (42% vs. 32%), hypertension (37% vs. 32%), diarrhea (36% vs. 29%), pneumonia (36% vs. 30%), dyspnea (29% vs. 24%), bronchitis (24% vs. 13%), and cough (23% vs. 15%). Serious adverse reactions that occurred in more than 5% of patients who received Sarclisa combination therapy were pneumonia (25%) and upper respiratory tract infections (9%). Permanent discontinuation of treatment because of adverse reactions (Grade 1-4) occurred in 8% of patients treated with Sarclisa combination therapy, and 2.8% of patients discontinued due to an infection.2

Multiple Myeloma: an incurable blood cancer, with significant burden

Multiple Myeloma (MM) is the second most common hematologic malignancy4, affecting more than 130,000 patients in the United States; approximately 32,000 Americans are diagnosed with multiple myeloma each year.5 Despite available treatments, MM remains an incurable malignancy, and is associated with significant patient burden. Since MM does not have a cure, most patients will relapse. Relapsed MM is the term for when the cancer returns after treatment or a period of remission. Refractory MM refers to when the cancer does not respond or no longer responds to therapy.

About Sarclisa

Sarclisa is a monoclonal antibody that binds to a specific epitope on the CD38 receptor on MM cells. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a potential target for antibody-based therapeutics such as Sarclisa.

This marks the second FDA approval for Sarclisa since March 2020 and comes more than three months ahead of the FDA’s target action date. In February, the European Medicines Agency’s Committee for Medicinal Products for Human Use adopted a positive opinion for a second indication for Sarclisa, in combination with carfilzomib and dexamethasone (Kd), for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. The use of Sarclisa in combination with Kd is not currently approved in the European Union (EU), but the final decision whether to expand the indication is expected from the European Commission in the coming months. In Europe, Sarclisa is indicated in combination with pom-dex for the treatment of adult patients with RRMM who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on the last therapy. Outside of the U.S. and the EU, Sarclisa is approved in Switzerland, Canada, Australia, Japan, Russia, the UAE, South Korea, Taiwan and Brazil in combination with pom-dex for the treatment of certain adults with RRMM.

Sarclisa continues to be evaluated in multiple ongoing Phase 3 clinical trials in combination with current standard and novel treatments across the MM treatment continuum. It is also under investigation for the treatment of other hematologic malignancies and solid tumors. The use of Sarclisa in these additional settings is currently under clinical investigation and its safety and efficacy have not been fully evaluated by any regulatory authority.

IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S. PATIENTS

What is SARCLISA?

SARCLISA is a prescription medicine used in combination with:

The medicines pomalidomide and dexamethasone, to treat adults who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor to treat multiple myeloma.
The medicines carfilzomib and dexamethasone, to treat adults with multiple myeloma who have already received 1 to 3 lines of treatment and they did not work or are no longer working.
It is not known if SARCLISA is safe and effective in children.

Important Safety Information

Do not receive SARCLISA if you have a history of a severe allergic reaction to isatuximab-irfc or any of the ingredients in SARCLISA (see the list of ingredients in the full Prescribing Information).

Before receiving SARCLISA, tell your healthcare provider about all of your medical conditions, including if you:

Have heart problems, if your healthcare provider prescribes SARCLISA in combination with carfilzomib and dexamethasone for you.
Are pregnant or plan to become pregnant. SARCLISA may harm your unborn baby. You should not receive SARCLISA during pregnancy.
Females who are able to become pregnant should use an effective method of birth control during treatment and for 5 months after your last dose of SARCLISA. Talk to your healthcare provider about birth control methods that you can use during this time.
Tell your healthcare provider right away if you think you are pregnant or become pregnant during treatment with SARCLISA.
Are breastfeeding or plan to breastfeed. It is not known if SARCLISA passes into your breast milk. You should not breastfeed during treatment with SARCLISA.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines. Especially tell your healthcare provider if you have ever taken a medicine for your heart.

How will I receive SARCLISA?

SARCLISA will be given to you by your healthcare provider by intravenous (IV) infusion into your vein.
SARCLISA is given in treatment cycles of 28 days (4 weeks), together with either the medicines pomalidomide and dexamethasone, or carfilzomib and dexamethasone.
In cycle 1, SARCLISA is usually given weekly.
Starting in cycle 2, SARCLISA is usually given every 2 weeks.
If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.
Your healthcare provider will give you medicines before each dose of SARCLISA to help reduce the risk of infusion reactions (make them less frequent and severe).
What are the possible side effects of SARCLISA?

SARCLISA may cause serious side effects, including:

Infusion reactions. Infusion reactions are common with SARCLISA and can sometimes be severe or life threatening.
Your healthcare provider will prescribe medicines before each infusion of SARCLISA to help decrease your risk for infusion reactions or to help make any infusion reaction less severe. You will be monitored for infusion reactions during each dose of SARCLISA.
Your healthcare provider may slow down or stop your infusion, or completely stop treatment with SARCLISA if you have an infusion reaction.
Get medical help right away if you develop any of the following symptoms of infusion reaction during or after an infusion of SARCLISA:

— shortness of breath, wheezing, or trouble breathing
— swelling of the face, mouth, throat, or tongue
— throat tightness
— palpitations
— dizziness, lightheadedness, or fainting
— headache
— cough
— rash or itching
— nausea
— runny or stuffy nose
— chills

Decreased white blood cell counts. Decreased white blood cell counts are common with SARCLISA and certain white blood cells can be severely decreased. You may have an increased risk of getting certain infections, such as upper and lower respiratory tract infections and urinary tract infections.

Your healthcare provider will check your blood cell counts during treatment with SARCLISA. Your healthcare provider may prescribe an antibiotic or antiviral medicine to help prevent infection, or a medicine to help increase your white blood cell counts during treatment with SARCLISA.
Tell your healthcare provider right away if you develop any fever or symptoms of infection during treatment with SARCLISA.

Risk of new cancers. New cancers have happened in people during treatment with SARCLISA. Your healthcare provider will monitor you for new cancers during treatment with SARCLISA.
Change in blood tests. SARCLISA can affect the results of blood tests to match your blood type. Your healthcare provider will do blood tests to match your blood type before you start treatment with SARCLISA. Tell all of your healthcare providers that you are being treated with SARCLISA before receiving blood transfusions.
Heart failure. Heart failure can happen during treatment with SARCLISA in combination with carfilzomib and dexamethasone. Tell your healthcare provider right away if you develop any of the following symptoms:
– trouble breathing

– cough

– swelling of your ankles, feet, or legs

The most common side effects of SARCLISA in combination with pomalidomide and dexamethasone include:

lung infection (pneumonia)
decreased red blood cell counts (anemia)
upper respiratory tract infection
decreased platelet counts (thrombocytopenia)
diarrhea
The most common side effects of SARCLISA in combination with carfilzomib and dexamethasone include:

upper respiratory tract infection
tiredness and weakness
high blood pressure
diarrhea
lung infection (pneumonia)
trouble breathing
trouble sleeping
bronchitis
cough
back pain
decreased red blood cells (anemia)
decreased platelet counts (thrombocytopenia)
These are not all the possible side effects of SARCLISA. For more information, ask your healthcare provider or pharmacist.

On March 31, 2021, CTI BioPharma Corp. (the "Company") reported that entered into an underwriting agreement (the "Underwriting Agreement") with Stifel Nicolaus & Company, Incorporated and JMP Securities LLC (the "Representatives"), as representatives of the underwriters named therein (the "Underwriters"), relating to the offer and sale (the "Offering") of 14,260,800 shares of the Company’s common stock, par value $0.001 per share (the "Common Stock"), at a public offering price of $2.50 per share , and 600 shares of the Company’s Series X1 convertible preferred stock, par value $0.001 per share (the "Series X1 Preferred Stock"), at a public offering price of $25,000 per share (Filing, 8-K, CTI BioPharma, MAR 31, 2021, View Source [SID1234577615]). In addition, the Company granted the Underwriters a 30-day option to purchase up to an additional 2,139,120 shares of its Common Stock on the same terms and conditions (the "Option"). On April 5, 2021, the Underwriters exercised the Option in full.

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The aggregate gross proceeds to the Company from the Offering and the Option are approximately $56.0 million, before deducting underwriting discounts and estimated offering expenses.

The securities described above were issued pursuant to the Company’s effective shelf registration statement on Form S-3 (File No. 333-251161) (the "Registration Statement"), filed with the Securities and Exchange Commission (the "SEC") on December 7, 2020 and declared effective on December 15, 2020. On March 31, 2021, the Company filed a prospectus supplement with the SEC in connection with the Offering. The Offering and the Option closed on April 6, 2021.

In the Underwriting Agreement, the Company agreed to indemnify the Underwriters against certain liabilities, including liabilities under the Securities Act of 1933, as amended, or to contribute payments that the Underwriters may be required to make because of such liabilities. The foregoing description of the Underwriting Agreement is not complete and is qualified in its entirety by references to its full text, a copy of which is filed as Exhibit 1.1 to this Current Report on Form 8-K and incorporated by reference herein.

On March 31, 2021 Tyra Biosciences, a biotech company targeting acquired resistance in oncology with purpose-built drugs, reported the closing of a $106 million Series B financing to accelerate and expand its in-house drug discovery platform, SNÅP, and to advance its pipeline of novel, small molecule therapies into the clinic (Press release, Tyra Biosciences, MAR 31, 2021, View Source [SID1234586908]).

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The financing is led by new investor Nextech Invest and includes participation from Cormorant Asset Management, BVF Partners, L.P., Janus Henderson Investors, and Logos, as well as returning investors Alta Partners, RA Capital, Boxer Capital of Tavistock Group, and Canaan. Melissa McCracken, Ph.D. from Nextech Invest will join the TYRA Board of Directors.

"We warmly welcome Melissa to our Board of Directors, and the addition of top-tier crossover investors to our strong financing syndicate," said Todd Harris, Founder and Chief Executive Officer of Tyra Biosciences. "At Tyra, we are driven to overcome the desperation faced by patients in the moment their therapy stops working. This financing enables the acceleration and expansion of our mission to deliver therapies that are purpose-built for each new acquired resistance, so that for patients living with cancer, there is always a new hope."

With this raise, TYRA also announces the expansion of its executive leadership team, including:
— Hiroomi Tada, MD, Ph.D., Chief Medical Officer
— Piyush Patel, Ph.D., Chief Development Officer; and
— Robert L. Hudkins, Ph.D., promoted to Chief Technology Officer.

"Tyra has assembled a dynamic and experienced team that is bringing unprecedented speed, clarity, and focus to structure-based drug discovery through purposeful process optimization and prioritization of real-world, empirical data," said Dr. McCracken, Principal at Nextech Invest. "I am pleased to join the Board of Directors at Tyra, which is well positioned to deliver on their vision of accelerating the development of new therapies targeting acquired resistance in oncology."

TYRA’s in-house discovery engine, SNÅP, enhances traditional structure-based drug discovery through the generation of rapid and sequential "structural SNÅPshots" that enable the empirical (observational) evaluation of atomic-level interactions between drug and target.

"At Tyra, we’ve built in-house tools and expertise to shorten the timeline for generating crystal structures, deep cellular profiles, and data from in vivo models to days rather than weeks," said Robert Hudkins, Ph.D., Chief Technology Officer at Tyra Biosciences. "This vast amount of empirical data forms comprehensive ‘structural SNÅPshots’ that we use to refine molecular designs down to the tenth of an angstrom on a weekly cycle."

The first drug candidates developed using the SNÅP platform are expected to be nominated for development in 2021 and advance to the clinic in 2022.

"The rigor, fidelity, and speed of the SNÅP platform drives rapid discovery cycles towards novel drug candidates differentiated through achieving precise structural fit to their targets," said Hiroomi Tada, MD, Ph.D., Chief Medical Officer at Tyra Biosciences. "I am excited to join Tyra at this early stage to ensure that this ethos is extended to our approach to clinical development as we relentlessly advance new therapies for patients."

On March 31, 2021 Istari Oncology, Inc., a clinical-stage biotechnology company, reported that the first patient was dosed in the LUMINOS-102 phase 2 clinical trial, which will assess the safety and efficacy of PVSRIPO alone or in combination with a programmed death receptor-1/ligand 1 (PD-1/L1) inhibitor in patients with melanoma who are resistant to these checkpoint therapies (Press release, Istari Oncology, MAR 31, 2021, View Source [SID1234577443]).

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PVSRIPO is a novel viral immunotherapy that activates the innate and adaptive immune system to stimulate the production of a functional, systemic anticancer CD8+ T cell response. Following positive phase 1 results,1 the phase 2 trial will further explore PVSRIPO’s impact on this population of patients in severe need of additional therapeutic options.

"Anti-PD-1/L1 therapies have been a major advancement in melanoma treatment, however, many patients develop resistance or never respond in the first place," said Matt Stober, President and Chief Executive Officer at Istari Oncology. "We are very optimistic about the prospects for the phase 2 trial. PVSRIPO monotherapy has already shown clinical activity in this population, and its mechanism is synergistic with anti-PD-1/L1 therapies, so we believe the combination may provide even more benefit."

"As the use of anti-PD-1/L1 therapies has grown, so too has the need for new treatments as patients experience primary or acquired resistance and must resort to therapeutic approaches with a high incidence of serious adverse events," said Garrett Nichols, MD, MS, Chief Medical Officer at Istari Oncology. "Our goal is to address this unmet need, and LUMINOS-102 will be a critical step in determining whether PVSRIPO can rekindle antitumor responses in the PD-1/L1 refractory population without adding any significant toxicity."

LUMINOS-102 is an open-label, phase 2, multicenter randomized trial (NCT04577807) in patients with melanoma that have progressed on anti–PD1/L1 therapy and will characterize the safety, tolerability and initial efficacy of PVSRIPO intratumoral injection alone (Arm 1) and in combination with a PD-1 inhibitor (Arm 2). An interim analysis is planned once 20 patients have been randomized and treated for 3 months. Patient outcomes, including objective response rates (by RECIST criteria), durability of responses, progression free survival and overall survival will be measured over a 24-month time frame.

LUMINOS-102 builds upon a successful phase 1 study of PVSRIPO monotherapy in anti–PD-1 refractory advanced melanoma presented by Dr. Georgia Beasley and colleagues at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2020 Annual Meeting and in-press for an upcoming issue of the Journal for ImmunoTherapy of Cancer (JITC). In the phase 1 study, the overall response rate in subjects who received three single intratumoral injections 3 weeks apart (the maximum number administered in the study) was 67% (4/6), suggesting PVSRIPO was able to initiate or rekindle responses in patients who have failed anti–PD-1 therapy. Responses were observed in both injected and noninjected tumors, suggestive of an abscopal response. No serious adverse events or dose-limiting toxicities were observed.

"Being based on the poliovirus vaccine, our team was intrigued by the potential for PVSRIPO to leverage an immunological recall response to fight cancer in patients who have been vaccinated against polio. This and other unique mechanisms as well as the responses seen in the phase 1 trial encouraged us to get involved in LUMINOS-102," noted Ding Wang, MD, ?Director of the Phase 1 Program and Associate Director of Clinical Trials Office at Henry Ford Cancer Institute, Detroit, MI. "LUMINOS-102 will build on these data and further evaluate the ability of PVSRIPO to generate a systemic immune response, important for patients with unresectable anti–PD-1 refractory melanoma. We’re proud to be the first site to treat a participant and looking forward to continuing enrollment."

The LUMINOS-102 phase 2 trial will be conducted across more than 20 research sites across the US including Henry Ford Cancer Institute.

For more information about Istari Oncology and their ongoing clinical trials, visit istarioncology.com.

About PVSRIPO
PVSRIPO is an investigational immunotherapy based on the live attenuated Sabin type 1 poliovirus vaccine that has been genetically modified for safety. PVSRIPO has a distinct target (the poliovirus receptor, CD155), which is expressed on virtually all solid tumors and antigen-presenting cells. Via CD155, PVSRIPO targets tumors with two primary mechanisms: 1) direct damage to and killing of cancerous cells; and 2) engaging innate and adaptive antitumor immune responses via nonlethal infection of antigen presenting cells in the tumor, which stimulates a specific signaling pathway resulting in a sustained, robust type-I/III interferon-dominant response, with minimal release of unwanted cytokines. Its effects are potentiated by prior vaccination against poliovirus. PVSRIPO has been granted Breakthrough Therapy Designation and Orphan Status by the FDA in recurrent glioblastoma. PVSRIPO has also been granted Orphan Status by the FDA for advanced melanoma.

About Melanoma
There are estimated to be over 12,000 new and recurrent cases of advanced, unresectable melanoma diagnosed in the U.S. each year, and around 7,000 deaths. While immune checkpoint inhibitors have dramatically improved the outlook for advanced melanoma patients today, most patients treated with these immunotherapies are either primary nonresponders or eventually develop immune-refractory progressive disease and require additional therapy.

On March 31, 2021 CTI BioPharma Corp. (Nasdaq: CTIC) ("CTI"), a biopharmaceutical company focused on the acquisition, development and commercialization of novel targeted therapies covering a spectrum of blood-related cancers, reported that it intends to offer and sell shares of its common stock and series X1 preferred stock (the "Series X1 Preferred") in an underwritten registered public offering (Press release, CTI BioPharma, MAR 31, 2021, View Source [SID1234577460]). All of the securities in the proposed offering are to be sold by CTI. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed, or the actual size or terms of the offering. Each share of Series X1 Preferred will be convertible into 10,000 shares of common stock at the election of the holder, subject to beneficial ownership conversion limits applicable to the Series X1 Preferred.

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CTI intends to use the proceeds from the proposed sale of its shares of common stock and Series X1 Preferred Stock for commercialization activities for pacritinib, general working capital and corporate purposes.

Stifel and JMP Securities are acting as joint book-running managers for the offering. BTIG is acting as lead manager for the offering.

The offering is being made pursuant to a registration statement on Form S-3 that was previously filed with the U.S. Securities and Exchange Commission (the "SEC") and subsequently was declared effective by the SEC. A preliminary prospectus supplement and accompanying base prospectus relating to and describing the terms of the offering will be filed with the SEC. Copies of the preliminary prospectus supplement and accompanying prospectus relating to these securities may also be obtained by sending a request to Stifel, Nicolaus & Company, Incorporated, Attention: Syndicate, One Montgomery St, Suite 3700, San Francisco, CA 94104, by telephone at (415) 364-2720 or by email at [email protected], or JMP Securities LLC, 600 Montgomery St, Suite 1100, San Francisco, CA 94111, Attn: Prospectus Department, telephone: 415-835-8900.

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