Since the pioneering work of Salmon and Durie, quantitative measures of tumor burden in multiple myeloma (MM) have been used to make clinical predictions and model tumor growth. However, such quantitative analyses have not yet been performed on large data sets from trials using modern chemotherapy regimens.
We analyzed a large set of tumor response data from three randomized controlled trials of bortezomib-based chemotherapy regimens (total sample size n=1,469 patients) to establish and validate a novel mathematical model of MM cell dynamics.
Treatment dynamics in newly diagnosed patients were most consistent with a model postulating two tumor cell subpopulations, "progenitor cells" and "differentiated cells". Differential treatment responses were observed with significant tumoricidal effects on differentiated cells and less clear effects on progenitor cells. We validated this model using a second trial of newly diagnosed patients and a third trial of refractory patients. When applying our model to data of relapsed patients, we found that a hybrid model incorporating both a differentiation hierarchy and clonal evolution best explains the response patterns.
The clinical data, together with mathematical modeling, suggest that bortezomib-based therapy exerts a selection pressure on myeloma cells that can shape the disease phenotype, thereby generating further inter-patient variability. This model may be a useful tool for improving our understanding of disease biology and the response to chemotherapy regimens.
Copyright ©2016, American Association for Cancer Research (AACR) (Free AACR Whitepaper).

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CD1d is a receptor on antigen-presenting cells involved in triggering cell populations, particularly natural killer T (NKT) cells, to release high levels of cytokines. NKT cells are implicated in asthma pathology and blockade of the CD1d/NKT cell pathway may have therapeutic potential. We developed a potent anti-human CD1d antibody (NIB.2) that possesses high affinity for human and cynomolgus macaque CD1d (KD ∼100 pM) and strong neutralizing activity in human primary cell-based assays (IC50 typically <100 pM). By epitope mapping experiments, we showed that NIB.2 binds to CD1d in close proximity to the interface of CD1d and the Type 1 NKT cell receptor β-chain. Together with data showing that NIB.2 inhibited stimulation via CD1d loaded with different glycolipids, this supports a mechanism whereby NIB.2 inhibits NKT cell activation by inhibiting Type 1 NKT cell receptor β-chain interactions with CD1d, independent of the lipid antigen in the CD1d antigen-binding cleft. The strong in vitro potency of NIB.2 was reflected in vivo in an Ascaris suum cynomolgus macaque asthma model. Compared with vehicle control, NIB.2 treatment significantly reduced bronchoalveolar lavage (BAL) levels of Ascaris-induced cytokines IL-5, IL-8 and IL-1 receptor antagonist, and significantly reduced baseline levels of GM-CSF, IL-6, IL-15, IL-12/23p40, MIP-1α, MIP-1β, and VEGF. At a cellular population level NIB.2 also reduced numbers of BAL lymphocytes and macrophages, and blood eosinophils and basophils. We demonstrate that anti-CD1d antibody blockade of the CD1d/NKT pathway modulates inflammatory parameters in vivo in a primate inflammation model, with therapeutic potential for diseases where the local cytokine milieu is critical.

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On March 23, 2016 Heat Biologics, Inc. ("Heat") (Nasdaq:HTBX), an immuno-oncology company developing novel therapies that activate a patient’s immune system against cancer, reported the closing of its previously announced underwritten public offering of 9,100,000 shares of its common stock and warrants to purchase up to an aggregate of 6,825,000 shares of its common stock at a combined public offering price of $0.75 per share and related warrant (Press release, Heat Biologics, MAR 23, 2016, View Source [SID:1234509847]). Each share of its common stock was sold together with a warrant to purchase 0.75 of a share of its common stock. The gross proceeds from this offering were approximately $6.8 million, before deducting the underwriting discount and estimated offering expenses payable by Heat, but excluding proceeds from the exercise of any warrants.

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Heat intends to use the net proceeds from the offering to complete its Phase 2 clinical trial evaluating HS-410 for the treatment of non-muscle invasive bladder cancer (NMIBC), which remains Heat’s primary focus. The remaining net proceeds are expected to be used to advance the current eight patients enrolled in Heat’s Phase 1b clinical trial evaluating HS-110 for the treatment of non-small cell lung cancer (NSCLC) through the reporting of topline data, as well as for licensing or acquisition of assets complementary to its existing programs and for general corporate and working capital purposes.

Roth Capital Partners and Aegis Capital Corp. acted as joint book-running managers and Noble Financial Capital Markets acted as co-manager for this offering.

The shares of common stock and warrants described above were offered pursuant to a registration statement on Form S-1 that was declared effective by the U.S. Securities and Exchange Commission on March 17, 2016 and a related automatically effective registration statement on Form S-1 filed pursuant to Rule 462(b) of the Securities Act of 1933, as amended.

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

On March 22, 2016 Eiger BioPharmaceuticals, Inc. (NASD: EIGR) reported completion of its merger with Celladon Corporation effective March 22, 2016 (Filing, 8-K, Celladon, MAR 23, 2016, View Source [SID:1234509850]). In connection with the merger, Celladon changed its name to Eiger BioPharmaceuticals, Inc. The combined company will commence trading as of the open of market March 23, 2016 on The NASDAQ Global Market under the symbol "EIGR."

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Prior to the merger, Eiger received gross proceeds of $39.5 million, including the conversion of $6.0 million in aggregate principal amount under, and all interest accrued on, convertible promissory notes of Eiger, in new investment from a combination of certain current and new investors in Eiger, including HBM Healthcare Investments, Vivo Capital, InterWest Partners, RA Capital Management, Sabby Management, Sphera Global Healthcare, Perceptive Advisors and Monashee Capital Partners. Together with approximately $26.1 million in available, pre-merger cash on Celladon’s balance sheet, the combined company has approximately $59 million in cash available before the payment of transaction and other fees.

"We are very pleased to complete this merger, which marks a significant milestone for Eiger. We are transitioning from a private company to a publicly-traded company through this merger, and significantly increasing our financial resources," said David Cory, President and CEO of Eiger. "These funds are expected to support operations and enable us to advance all four Phase 2 Orphan Disease programs."

Following the previously announced financing and merger and 1-for-15 reverse stock split of its outstanding common stock in connection with the merger, the combined company has approximately 7.0 million shares of common stock outstanding.
Jefferies LLC acted as lead placement agent, Piper Jaffray acted as placement agent and Oppenheimer acted as financial advisor on the financing. Additionally, Jefferies LLC acted as lead financial advisor and Piper Jaffray acted as financial advisor on the merger.

On March 23, 2016 Sophiris Bio Inc. (NASDAQ: SPHS) (the "Company" or "Sophiris"), a biopharmaceutical company developing topsalysin (PRX302) for the treatment of urological diseases, reported financial results for the three months and year ended December 31, 2015 (Press release, Sophiris Bio, MAR 23, 2016, View Source [SID:1234509857]).

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"Compelling data have been announced from both topsalysin programs over the past few months. Topsalysin demonstrated promising therapeutic activity in four of the initial seven patients with localized prostate cancer – including one with a complete tumor ablation. This encouraging data follows the announcement in November of 2015 that topsalysin met the primary endpoint in a Phase 3 study in BPH," stated Randall Woods, president and CEO of Sophiris Bio. "We believe that these robust and consistent BPH results will help us secure the capital needed to advance the BPH program into the final clinical study required for marketing approval, in a non-dilutive manner such as through a development and/or commercial partner."

Liquidity:

At December 31, 2015, we had cash, cash equivalents and securities available-for-sale of $8.4 million and net working capital of $5.6 million. We expect that our cash, cash equivalents and securities available-for-sale as of December 31, 2015 will be sufficient to fund our operations through September 2016 assuming that we do not initiate any additional clinical development of topsalysin beyond our on-going Phase 2a proof of concept study in localized prostate cancer. We will need to obtain additional capital to fund a second Phase 3 clinical trial of topsalysin for the treatment of the symptoms of BPH and for any future clinical development of topsalysin for the treatment of localized prostate cancer beyond our ongoing Phase 2a proof of concept clinical trial and to fund our ongoing operations. As of December 31, 2015, the outstanding principal balance of our term loan was $5.3 million on which we make principal and interest payments monthly.

Business Highlights:

Topsalysin BPH Program:

On November 10, 2015, the Company announced final positive results from its Phase 3 "PLUS-1" study of topsalysin (PRX302) as a treatment for lower urinary tract symptoms of benign prostatic hyperplasia (BPH, enlarged prostate)
Topsalysin met the primary endpoint of the study, demonstrating a statistically significant improvement in International Prostate Symptom Score (IPSS) total score from baseline over 12 months compared to the vehicle-only control group, (p = 0.043).
The clinical relevance of the overall improvement in IPSS was assessed by an additional efficacy endpoint, the patient self-assessment of the impact of treatment on their quality of life. Patients reported a sustained improvement in their quality of life from Weeks 18 through 52, which was statistically significantly superior to patients treated with vehicle for every post-baseline visit beginning at week 18 (reaching p = 0.004).
Topsalysin continues to have an attractive safety profile, with no evidence of any treatment related sexual or cardiovascular side effects.
Topsalysin Localized Prostate Cancer Program:

As of December 31, 2015, a total of 18 patients with clinically significant, localized low to intermediate risk prostate cancer (prostate cancer that has not yet metastasized) had been enrolled in the ongoing Phase 2a proof of concept study.
On January 28, 2016, the Company announced that a review of the 6-month biopsy data from the first seven patients to complete the study showed that four patients experienced a response to treatment: One patient experienced complete ablation of the tumor where no evidence of the treated tumor remained on a targeted biopsy at 6 months; three patients experienced either a reduction in the maximum cancer core length or a reduction in Gleason pattern; three patients had no response to treatment.
The Company held a conference call to review clinical data with principal investigators from the BPH program and the prostate cancer program, which can be accessed at View Source
The Company expects to have final data on all patients by the end of second quarter of 2016.
Woods added, "Practicing urologists view topsalysin as a compelling alternative for their BPH patients who have discontinued their oral medications and are unwilling to take the leap to the more invasive surgical procedures. Given the convenience of this four minute administration of topsalysin in the urologist’s office, 12 months of benefit and a benign safety profile, we believe topsalysin has the potential to obtain a significant position within the BPH treatment paradigm."

Financial Results:

For the fourth quarter ended December 31, 2015

The Company reported a net loss of $2.5 million ($0.15 per share) for the three months ended December 31, 2015 compared to a net loss of $5.3 million ($0.31 per share) for the three months ended December 31, 2014.

Research and development expenses

Research and development expenses were $1.7 million for the three months ended December 31, 2015 compared to $4.1 million for the three months ended December 31, 2014. The decrease in research and development costs is attributable to decreases in the costs associated with the Company’s completed Phase 3 PLUS-1 clinical trial of topsalysin, costs associated with the manufacturing activities for topsalysin and personnel related costs. These decreases are partially offset by an increase in costs associated with the Phase 2a proof of concept clinical trial for localized low to intermediate risk prostate cancer which enrolled its first patient in the second quarter of 2015.

General and administrative expenses

General and administrative expenses were $0.7 million for the three months ended December 31, 2015 compared to $1.0 million for the three months ended December 31, 2014. The decrease is primarily due to a decrease in non-cash stock-based compensation expense, consulting, and personnel related costs.

For the year ended December 31, 2015

The Company reported a net loss of $14.2 million ($0.84 per share) for the year ended December 31, 2015 compared to a net loss of $30.7 million ($1.85 per share) for the year ended December 31, 2014.

Research and development expenses

Research and development expenses were $9.9 million for the year ended December 31, 2015 compared to $24.7 million for the year ended December 31, 2014. The decrease in research and development costs is attributable to decreases in the costs associated with the Company’s Phase 3 PLUS-1 clinical trial of topsalysin, costs associated with the manufacturing activities for topsalysin and personnel related costs. These decreases are partially offset by an increase in costs associated with the Phase 2a proof of concept clinical trial for localized low to intermediate risk prostate cancer.

General and administrative expenses

General and administrative expenses were $3.6 million for the year ended December 31, 2015 compared to $5.3 million for the year ended December 31, 2014. The decrease is primarily due to a decrease in non-cash stock based compensation expense and, to a lesser extent, decreases in legal, travel, professional, consulting, and personnel related costs.