The Exit Theory of Judicial Appraisal

For many years, we and other commentators have observed the problem with allowing judges wide discretion to fashion appraisal awards to dissenting shareholders based on widely divergent, expert valuation evidence submitted by the litigating parties. The results of this discretionary approach to valuation have been to make appraisal litigation less predictable and therefore more costly and likely. While this has been beneficial to professionals who profit from corporate valuation litigation, it has been harmful to shareholders, making deals costlier and less likely to be completed. In this Article, we propose to end the problem of discretionary judicial valuation by tracing the origins of the appraisal remedy and demonstrating that its true purpose has always been to protect the exit rights of minority shareholders when a cash exit is otherwise unavailable, and not to judge the value of the deal. Judicial appraisal should not be a remedy for dissenting shareholders when a market exit or equivalent protection is otherwise available. While such reform would be costly to valuation litigation professionals, their loss would be more than offset by the benefit of such reforms to shareholders involved in future corporate transactions. Shareholders presently have adequate protections, both from private arrangements and legal doctrines involving fiduciary duties

The Death of Appraisal Arbitrage: Ending Windfalls for Deal Dissenters

In this article, we take note of a new and positive development in Delaware\u27s law of appraisal: more robust enforcement of Section 262(h), which expressly excludes from fair value in appraisal litigation the value that is uniquely associated with the deal from which the shareholders seeking appraisal are dissenting. For public firms, this implies that deal dissenters are entitled to no more than the price that prevailed prior to the deal\u27s announcement. In a salutary development, the Delaware Chancery Court took this approach in its recent appraisal decision in Verition Master Fund Partners, Ltd. v. Aruba Networks, Inc., awarding to the deal dissenters the pre-announcement price and striking a blow against appraisal arbitrage —a trading and litigation strategy that is predicated on deal dissenters receiving appraisal remedies in excess of the deal prices from which they dissent. We explore here the historical and economic rationales for limiting the appraisal remedy in this fashion. And we conclude with some recommendations for ending or limiting appraisal windfalls in the context of private firms as well via contractual and corporate bylaw valuation mechanisms that would replace judicial with market valuation in appraisal litigation as well as select litigation fora that would be amenable to enforcement of such mechanisms

Colonic ulcerations may predict steroid-refractory course in patients with ipilimumab-mediated enterocolitis

To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line therapy

Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis

BackgroundDespite unprecedented efficacy across multiple tumor types, immune checkpoint inhibitor therapy is associated with a unique and wide spectrum of immune‐related adverse events (irAEs), including neurologic events ranging from mild headache to potentially life‐threatening encephalitis. Here, we summarize neurologic irAEs associated with nivolumab and ipilimumab melanoma treatment, present cases of treatment‐related encephalitis, and provide practical guidance on diagnosis and management.MethodsWe searched a Global Pharmacovigilance and Epidemiology database for neurologic irAEs reported over an 8‐year period in patients with advanced melanoma receiving nivolumab with or without ipilimumab from 12 studies sponsored by Bristol‐Myers Squibb. Serious neurologic irAEs were reviewed, and relationship to nivolumab or ipilimumab was assigned.ResultsIn our search of 3,763 patients, 35 patients (0.93%) presented with 43 serious neurologic irAEs, including neuropathy (n = 22), noninfective meningitis (n = 5), encephalitis (n = 6), neuromuscular disorders (n = 3), and nonspecific adverse events (n = 7). Study drug was discontinued (n = 20), interrupted (n = 8), or unchanged (n = 7). Most neurologic irAEs resolved (26/35 patients; 75%). Overall, median time to onset was 45 days (range 1–170) and to resolution was 32 days (2–809+). Median time to onset of encephalitis was 55.5 days (range 18–297); four cases resolved and one was fatal.ConclusionBoth oncologists and neurologists need to be aware of signs and symptoms of serious but uncommon neurologic irAEs associated with checkpoint inhibitors. Prompt diagnosis and management using an established algorithm are critical to minimize serious complications from these neurologic irAEs.Implications for PracticeWith increasing use of checkpoint inhibitors in cancer, practicing oncologists need to be aware of the potential risk of neurologic immune‐related adverse events and be able to provide prompt treatment of this uncommon, but potentially serious, class of adverse events. We summarize neurologic adverse events related to nivolumab alone or in combination with ipilimumab in patients with advanced melanoma from 12 studies and examine in depth 6 cases of encephalitis. We also provide input and guidance on the existing neurologic adverse events management algorithm for nivolumab and ipilimumab.Melanoma is a particularly immunogenic cancer, and immune checkpoint inhibitors have been extensively studied in this tumor type. This review focuses on the incidence of serious neurologic immune‐related adverse events, specifically encephalitis, in patients with advanced melanoma treated with nivolumab alone or in sequence or combination with ipilimumab. Practical guidance is provided for the diagnosis and management of treatment‐related encephalitis associated with nivolumab and ipilimumab.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139998/1/onco12130.pd

Open-label, randomized, multi-center study comparing the sequence of high dose Aldesleukin (Proleukin® (HD IL-2) and Ipilimumab Yervoy® ) in patients with metastatic melanoma (proclivity 02)

Purpose: To investigate whether the sequence of HD IL-2 and a checkpoint inhibitor, Ipilimumab, will have additive or synergistic efficacy or toxicity when used in rapid sequence. Schema: Adult patients with Stage IV or unresectable Stage III metastatic melanoma who are eligible to receive HD IL-2, treatment naïve or have received prior adjuvant therapy are randomized to a sequential administration of 4 doses of Ipilimumab or 4 cycles of HD IL-2 dosed according to their package inserts. Fifty of the patients will start with one drug and 50 the other. The second drug will begin as soon as practically possible, without waiting for relapse. Entry criteria have recently been amended to include prior treatment with anti-PD-1 or anti-PDL-1. Twelve US sites are currently enrolling patients. An independent Data and Safety Monitoring Committee oversees the study. The primary endpoint is the proportional one year survival in the ITT population and a protocol defined population of patients who have received at least half of the planned doses of both study drugs. Clinical response and progression free survival will also be assessed. The primary endpoint is the proportional one year survival in the ITT population and a protocol defined population of patients who have received at least half of the planned doses of both study drugs. Clinical response and progression free survival will also be assessed. Current status: Twelve US sites are currently enrolling patients. To date 16 patients have been enrolled, 9 on the Ipilimumab first and 7 on the HD IL-2 first arms. No synergistic toxicity has been observed, but one death occurred in the HD IL-2 arm and one colectomy on the Ipilimumab arm, both prior to administration of the other drug

Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab.

The mechanisms by which immune checkpoint blockade modulates tumor evolution during therapy are unclear. We assessed genomic changes in tumors from 68 patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation (CA209-038 study). Tumors were analyzed by whole-exome, transcriptome, and/or T cell receptor (TCR) sequencing. In responding patients, mutation and neoantigen load were reduced from baseline, and analysis of intratumoral heterogeneity during therapy demonstrated differential clonal evolution within tumors and putative selection against neoantigenic mutations on-therapy. Transcriptome analyses before and during nivolumab therapy revealed increases in distinct immune cell subsets, activation of specific transcriptional networks, and upregulation of immune checkpoint genes that were more pronounced in patients with response. Temporal changes in intratumoral TCR repertoire revealed expansion of T cell clones in the setting of neoantigen loss. Comprehensive genomic profiling data in this study provide insight into nivolumab\u27s mechanism of action

Will Aruba Finish Off Appraisal Arbitrage and End Windfalls for Deal Dissenters? We Hope So

(Excerpt) The corporate law world has been abuzz of late about the commendable effort by Delaware’s courts to scale back “appraisal arbitrage”: a trading strategy predicated on deal dissenters receiving via appraisal litigation more for their shares than the deal prices from which they dissent. For years, parties engaging in appraisal arbitrage enjoyed the opportunity to initiate essentially risk free appraisal litigation with substantial upside potential, because it was assumed by courts and litigants that “fair value” entitled dissenters to at least the price of the deal they were rejecting and potentially more. But happily, this misunderstanding and misapplication of the law of appraisal now appears finally to have reached its end

The Death of Appraisal Arbitrage: Ending Windfalls for Deal Dissenters

In this article, we take note of a new and positive development in Delaware\u27s law of appraisal: more robust enforcement of Section 262(h), which expressly excludes from fair value in appraisal litigation the value that is uniquely associated with the deal from which the shareholders seeking appraisal are dissenting. For public firms, this implies that deal dissenters are entitled to no more than the price that prevailed prior to the deal\u27s announcement. In a salutary development, the Delaware Chancery Court took this approach in its recent appraisal decision in Verition Master Fund Partners, Ltd. v. Aruba Networks, Inc., awarding to the deal dissenters the pre-announcement price and striking a blow against appraisal arbitrage —a trading and litigation strategy that is predicated on deal dissenters receiving appraisal remedies in excess of the deal prices from which they dissent. We explore here the historical and economic rationales for limiting the appraisal remedy in this fashion. And we conclude with some recommendations for ending or limiting appraisal windfalls in the context of private firms as well via contractual and corporate bylaw valuation mechanisms that would replace judicial with market valuation in appraisal litigation as well as select litigation fora that would be amenable to enforcement of such mechanisms

The Exit Theory of Judicial Appraisal

For many years, we and other commentators have observed the problem with allowing judges wide discretion to fashion appraisal awards to dissenting shareholders based on widely divergent, expert valuation evidence submitted by the litigating parties. The results of this discretionary approach to valuation have been to make appraisal litigation less predictable and therefore more costly and likely. While this has been beneficial to professionals who profit from corporate valuation litigation, it has been harmful to shareholders, making deals costlier and less likely to be completed. In this Article, we propose to end the problem of discretionary judicial valuation by tracing the origins of the appraisal remedy and demonstrating that its true purpose has always been to protect the exit rights of minority shareholders when a cash exit is otherwise unavailable, and not to judge the value of the deal. Judicial appraisal should not be a remedy for dissenting shareholders when a market exit or equivalent protection is otherwise available. While such reform would be costly to valuation litigation professionals, their loss would be more than offset by the benefit of such reforms to shareholders involved in future corporate transactions. Shareholders presently have adequate protections, both from private arrangements and legal doctrines involving fiduciary duties